Hydatid Disease of The Brain Parenchyma: A Systematic Review

Abstarct

Introduction

Isolated brain hydatid disease (BHD) is an extremely rare form of echinococcosis. A prompt and timely diagnosis is a crucial step in disease management. This study is a systematic review of studies on intra-parenchymal BHD.

Methods

Studies that had the following properties were included: 1) The intra-parenchymal brain infection had been confirmed by diagnostic modalities, surgical findings, or histopathology. 2) The patient details were provided in the study. 3) The cystic lesion [s] were located intracranially.

Results

Altogether, 112 studies with a sample size of 178 cases met the inclusion criteria. Males (60.1%) showed a higher prevalence of the disease than females (38.2%). Most of the cases (64%) were affected during the first and second decades of their lives. Left-side multi-lobe involvement was the most common type of involvement (28.1%), followed by right-side multi-lobe involvement (26.4%). Surgery was the primary treatment option (97.2%), with the Dowling technique or the modified Arana-Iniguez method as the preferred approach. The total recurrence and mortality rates were 7.3% and 3.4%, respectively.

Conclusion

The definitive treatment for BHD is surgery, with the aim of removing cysts intact or excising mass lesions completely. A history of cyst rupture during operation may increase the likelihood of recurrence, and an extensive follow-up is required.

Introduction

Hydatid disease (HD) is a parasitic infection caused by the larvae of the tapeworm Echinococcus. Different genera of this microorganism can cause disease; however, in humans, two species have major clinical sequelae. Echinococcus granulosus results in cystic disease, the most common type, while Echinococcus multilocularis causes alveolar echinococcosis (AE), presenting as a mass or cystic lesion. The latter form of the disease is more invasive and aggressive, accompanied by numerous diagnostic and management challenges [1-3]. The most common organs affected by hydatidosis are the liver and lungs. However, other parts of the body can also be affected, including the bones, pericardium, orbits, ovaries, central nervous system (CNS), and other organs. In the literature, 2–3% of cases show involvement of the CNS.  The incidence of isolated brain involvement is reported to be 1–2% of all cases of echinococcosis, representing approximately 2% of all intracranial space-occupying lesions [4-6]. Brain hydatid disease (BHD) is endemic in many regions where livestock raising is prevalent, and human-animal contact is common. The incidence varies geographically, with higher rates reported in rural areas. However, globalization and increased travel have led to sporadic cases being reported in non-endemic regions as well. Humans can become infected through the ingestion of parasite eggs in contaminated food, water, or by direct contact with infected dogs, canines, and sheep [7,8]. Most cases of intracerebral echinococcosis are diagnosed in pediatrics (50-75%) [9]. The clinical presentation of hydatidosis depends on the patient's age, the size, number, and location of the cyst, as well as the host's immune system. Patients with HD can remain asymptomatic for long periods, as the lesions take years to develop. When they grow well, intracranial hypertension secondary to the mass effect on the surrounding tissues is usually the first clinical sign of brain involvement. The disease may not cause focal neurological signs until they become enlarged [10-12]. In the literature, several reviews have been published on cerebral HD; however, there is a scarcity of systematic reviews on the topic. This study is a systematic review of studies on intra-parenchymal BHD published over the last two decades [1-112].

Methods

Study design and reporting standards

The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Search strategy

A systematic review of all published studies on brain parenchymal HD was conducted from 2000 to 2024 using the following databases: Google Scholar, PubMed/MEDLINE, Cochrane Library, Science Direct, and EMBASE. The keywords used in the search included:

[brain OR intraparenchymal OR cerebral OR intracerebral OR cerebrum] AND [hydatid OR hydatidosis OR echinococcoses OR echinococcosis OR echinococcal OR echinococcus].

Eligibility criteria

Non-English language studies and those unrelated to humans were excluded before or during the initial screening. Studies of BHD were included if: 1) Diagnostic modalities, surgical findings, or histopathology confirmed the intraparenchymal brain infection. 2) Patient details were provided in the study. 3) Studies published in predatory journals (inappropriately peer-reviewed) and those not meeting inclusion criteria were excluded [113].

Study selection

Titles and abstracts of identified studies were initially screened, followed by full-text screening to assess eligibility.

Data extraction

Data extracted from eligible studies included study design, country of study, patient age, gender, residency, symptoms, medical history of HD, cyst characteristics, diagnosis, management, follow-up, and outcomes.

Data analysis

Data were analyzed qualitatively (descriptive analysis) using the Statistical Package for the Social Sciences (SPSS) version 27.0 software

Results

In total, 318 studies were obtained from the resources. Before any screening, 38 of them were directly excluded due to duplication, non-English language, non-articles, and animal studies. Following the initial screening, 92 studies did not meet the inclusion criteria and were excluded. The remaining 188 studies underwent full-text screening, and 122 of them were assessed for eligibility. Ultimately, 112 studies (comprising 178 cases) met the inclusion criteria (Figure 1). The characteristics of the included studies are shown in Table 1. Out of these studies, 101 (90.2%) were case reports, 10 (8.9%) were case series, and one (0.9%) was a retrospective cohort study. Most of the cases were reported in Turkey (24.1%), followed by Iran (16.7%), India (15.2%), and Morocco (9.8%). Males (60.1%) showed a higher prevalence of the disease than females (38.2%). Most of the cases (64%) occurred in the first and second decades of life, with a mean age of 20.44 ± 16.76 years. There were 71 cases (39. 9%) in rural areas and eight cases (4.5%) in urban areas. The residency of the remaining 99 cases (55.6%) was not reported. The type of the disease was cystic in 158 cases (88.8%) and alveolar in 20 cases (11.2%). Thirteen (7.3%) cases had a previous history of HD. The most commonly presented symptoms were signs of raised intracranial pressure, including headache (62.9%), vomiting (43.3%), followed by seizure (30.3%) and paresis (28.7%). Multiple organ involvement was present in 48 (27%) cases, involving the lung, liver, kidney, adrenal gland, blood vessels, or bones. The disease was primary with a single cyst or lesion in 118 patients (66.3%), primary with multiple cysts in 27 (15.1%), secondary with a single cyst in 23 (13%), and secondary with multiple cysts in 10 (5.6%). Left-side multi-lobe involvement was the most common type of involvement (28.1%), followed by right-side multi-lobe involvement (926.4%) and parietal lobe involvement (18.5%).

Serology had been done in 55 cases (30.9%), and it was positive in 34 (19.1%). Computed tomography scans (CT) or magnetic resonance imaging (MRI) were used in all cases. Surgery was the main treatment option (97.2%). The Dowling technique, or modified Arana-Iniguez, was the method of choice (95.5%). Surgery in three cases (1.7%) was done through the Burr-hole technique instead of open craniotomy. Conservative management was performed in five cases (2.8%). The patients underwent follow-up with a mean interval of one year. Recurrence was reported in 13 cases (7.3%). Among those, six cases (46.1 %) had intra-operative complications of traumatic rupture of the cyst, and two cases (15.4 %) had a surgical puncture of the cyst. The remaining five cases (38.5%) did not experience any intraoperative complications. The mortality rate was 3.4% (Table 2).

Table 1. Raw data of the included studies.

Author

Country

Study design

No

Age

Sex

Presenting symptoms

Imaging

ISHC

No. of cyst [s] in brain

Location of cyst [s] in brain

Size [cm]

Serology

Type of management

Pre-Op  complication

Intra-Op complication

Post-Op complication

Adjuvant therapy

Follow up* outcome

Svrckova et al [1]

United Kingdom

Case report

3

30

M

Headache, seizure

MRI

Yes

>1

Right parietal, right temporal

N/A

Positive

Conservative [Albendazole/praziquantel/steroid/antiepileptic]

N/A

N/A

N/A

None

Improved

26

M

Collapse, slurred speech, seizure, left side hemiparesis

CT, MRI

Yes

1

Right parietal and basal ganglia

N/A

Positive

Conservative [Albendazole/Praziquantel/steroid/Antiepileptic]

N/A

N/A

N/A

None

Improved

37

M

Dry cough

MRI

Yes

>1

Bilateral hemisphere

N/A

Positive

Conservative [Albendazole]

N/A

N/A

N/A

None

Improved

Altibi et al [2]

Brazil

Case report

1

13

M

Headache, nausea

CT, MRI

Yes

1

Right parieto-occipital

4.7

Negative

Surgical removal [Dowling]/neuronavigation

None

None

None

N/A

N/A

Casulli et al [3]

Italy

Case report

1

6

M

Right side hemiparesis

CT, MRI

Yes

1

Left fronto-parietal

6.8

Negative

Surgical removal/neuronavigation

None

None

Seizure, headache, worsened right hemiparesis, peri-lesional edema

Albendazole, Antiepileptic,Steroid

Improved

Lakhdar et al [4]

Morocco

Case report

1

30

M

Headache, right side hemiparesis

MRI

Yes

>1

Left fronto-parietal

N/A

Negative

Surgical removal

None

Rupture of cysts

None

Albendazole, Antibiotics, Antiepileptic

Recovered

Fariba Bi.  [5]

Iran

Case report

1

18

F

Headache, nausea, vomiting

MRI

Yes

1

Right temporal

N/A

N/A

Surgical removal

None

None

None

Albendazole, anticonvulsant

Recovered

Saleh et al [6]

Egypt

Case series

4

9

M

Drowsiness, vomiting, blurred vision, headache

CT, MRI

Yes

>1

Right parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

10

M

Seizure

CT, MRI

Yes

1

Right frontal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

12

M

Seizure

CT, MRI

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

14

F

Headache

CT, MRI

Yes

1

Right parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Alomari et al [7]

Saudi Arabia

Case report

1

8

F

Bilateral exophthalmos, blurred vision, headache

CT

Yes

1

Left frontal

15.3

Negative

Surgical removal [Dowling]

None

None

Seizure

Albendazole

Recovered

Hafedh et al [8]

Iraq

Case report

1

27

M

Seizure, headache, left side hemiparesis

CT, MRI

Yes

1

Right hemisphere

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Umut et al [9]

Turkey

Case report

1

14

M

Double vision, headache nausea, vomiting

MRI

Yes

2

Left occipital lobe, right insula

1st: 5.6  2nd:2.6

Negative

Surgical removal [Dowling] first occipital cysts and after 6 m temporal insula

None

None

None

Albendazole

Recovered

Çavusoglu et al [10]

India

Case report

1

8

F

Left side hemiparesis, left side mouth deviation, slurred speech

CT, Contrast MRI

Yes

1

Left fronto-parietal

10.2

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Garg et al [11]

India

Case report

1

8

F

Left side hemiparesis, left side mouth deviation, slurred speech

CT, Contrast MRI

Yes

1

Left fronto-parietal

10.2

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Raouzi et al [12]

Morocco

Case series

4

14

M

Seizure

CT, MRI

Yes

1

Right parietal area

N/A

Negative

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

4

M

Headache, vomiting

CT, MRI

Yes

1

Right fronto-parietal

7.05

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

3

M

Seizure

CT, MRI

Yes

1

Right parietal lobe

N/A

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

22

F

Seizure

CT, MRI

Yes

>1

Left fronto-parietal

N/A

Negative

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Assefa et al.  [13]

Ethiopia

Case series

4

8

M

Hemiparesis, nausea and vomiting

Contrast CT

Yes

1

Left fronto-parietal + daughter cyst

N/A

N/A

Surgical Removal

None

Rupture of Cyst

Cystic abscess, peri-cystic vasogenic edema

N/A

Recurrence

5

F

Hemiparesis, nausea and vomiting

Contrast CT

Yes

1

Right fronto-parietal

N/A

N/A

Surgical Removal

None

None

None

N/A

N/A

10

F

Hemiparesis, nausea and vomiting

Contrast MRI

Yes

1

Right parietal

N/A

N/A

Surgical Removal

None

None

None

N/A

N/A

29

M

Hemiparesis, nausea and vomiting

Contrast MRI

Yes

1

Right parietal

N/A

N/A

Surgical Removal

None

None

None

N/A

N/A

Tanki et al [14]

India

Case series

9

10

M

Seizure

CT, MRI

Yes

1

Right frontal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

12

F

Headache, nausea, vomiting, hemiparesis

CT, MRI

Yes

>1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

Rupture of Cyst

N/A

Albendazole

Recurrence

12

M

Seizure, headache, nausea, vomiting

CT, MRI

Yes

1

Right parietal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

10

M

Headache, nausea, vomiting

CT, MRI

Yes

1

Left parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

11

M

Seizure, hemiparesis

CT, MRI

Yes

1

Right parietal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

16

F

Seizure

CT, MRI

Yes

1

Left frontal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

14

M

Seizure, hemiparesis

CT, MRI

Yes

>1

Right parietal

N/A

N/A

Surgical removal [Dowling]

None

Rupture of Cyst

N/A

Albendazole

Recurrence

7

F

Seizure

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

12

F

Seizure, hemiparesis

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

None

N/A

Albendazole

Recovered

Noori et al [15]

Iraq

Case report

1

26

M

Headache, nausea, vomiting

CT

Yes

1

Right temporo-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

N/A

N/A

Haradhan et al [16]

Bangladesh

Case report

1

14

M

Headache

Contrast CT, Contrast MRI

Yes

1

Right fronto-parietal

12.48

N/A

Surgical removal

None

None

Right frontoparietal subdural hygroma, hydrocephalus, pseudocyst

Albendazole

N/A

Panda et al [17]

India

Case report

1

4

M

Seizure

CT, MRI

Yes

1

Left fronto-parietal

4.47

N/A

Surgical removal [Dowling]

None

Rupture of Cyst

None

N/A

N/A

Sharifi et al [18]

Iran

Case report

1

44

M

Mood swings, restlessness, and headache

CT

Yes

1

Right frontoparietal lobe

N/A

N/A

Surgical removal

None

None

None

Albendazole

N/A

Aydin et al [19]

Turkey

Case series

2

9

F

Headache, vomiting, bilateral decreased vision, left side tremor, left side hemiparesis

CT, MRI

Yes

1

Right fronto-temporo-parietal

9.81

Negative

Surgical removal [cavity placed balloon/ Dowling]

None

None

None

N/A

N/A

18

M

Headache, vomiting, blurred vision, fever, quadriparesis

CT, MRI

Yes

1

Right fronto-temporo-parietal

8.96

Negative

Surgical removal [cavity placed balloon/ Dowling-Orlando]

None

None

None

N/A

Recovered

Çakir et al  [20]

Turkey

Case report

1

6

M

Headache

MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

Cardiac arrest/death

N/A

N/A

Death

Ponnambath et al   [21]

India

Case report

1

40

M

Headache, seizure

Contrast MRI

No

1

Left occipital lobe

3

N/A

Surgical removal/neuronavigation

None

None

None

Albendazole

Minimal visual field defect

İzgi et al [22]

Turkey

Case report

1

5

M

Headache, nausea, vomiting, deviation of the eyes

MRI

Yes

1

Right parietal lobe

6.92

N/A

Surgical removal [Dowling]

None

None

None

N/A

N/A

El Ouarradi et al [23]

Morocco

Case report

1

11

M

Nausea, vomiting

CT

Yes

1

Right fronto-parieto-temporal lobe

9.75

Positive

Surgical removal [Dowling]

None

Shock/cardiac arrest/death

N/A

N/A

Death

Baboli et al [24]

Iran

Case report

1

19

M

Headache, left hemiparesis

Contrast MRI

Yes

1

Right fronto-parietal lobe

8

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Arega et al [25]

Ethiopia

Case report

1

8

F

Headache, vomiting

Contrast MRI

Yes

1

Right temporal

13.27

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Altaş et al [26]

Turkey

Case report

1

26

F

Headache, nausea, vomiting

Contrast CT, MRI

Yes

1

Right parieto-occipital

7.95

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Madeo et al [27]

USA

Case report

1

82

F

Emergency case

CT, MRI

Yes

1

Left hemisphere

4.08

Positive

Conservative [Albendazole]

N/A

N/A

N/A

None

Stable cyst

Menschaert et al [28]

Morocco

Case report

1

5

F

Seizures

MRI

Yes

1

Left parietal

N/A

Positive

Surgical removal

None

Puncture of Cyst

None

Albendazole

Learning disabilities

Şule et al [29]

Turkey

Case report

1

83

M

Headache, forgetfulness

Contrast MRI

No

1

Right frontal lobe

4

N/A

Surgical removal

None

None

None

N/A

N/A

Benhayoune et al [30]

Morocco

Case report

1

18

F

Headache, vomiting, seizure

Contrast MRI

No

1

Right parieto-occipital

7.9

N/A

Surgical removal [Arana]

None

None

None

Albendazole, Antiepileptic

Recovered

Vikaset al [31]

India

Case report

1

20

M

Seizure, right side paresthesia, headache, vomiting

Contrast CT, contrast MRI

Yes

>1

Left fronto-parietal

N/A

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Reddy et al  [32]

India

Case report

1

35

F

Headache, vomiting, altered sensorium, loss of consciousness

Contrast CT

Yes

5

Both parietal lobes

N/A

N/A

Surgical removal

None

None

None

N/A

Recovered

Al-Rawi et al  [33]

Iraq

Case series

8

3.5

F

N/A

CT

Yes

1

Left parietal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

7

F

N/A

CT

Yes

1

Right parietal

N/A

N/A

Surgical removal

None

Rupture of Cyst

Delayed recovery

Antiepileptic

Recurrence

11

M

N/A

CT

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

13

F

N/A

CT

Yes

1

Right frontal lobe

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

15

M

N/A

CT

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

15

M

N/A

CT

Yes

1

Right fronto-parietal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

35

M

N/A

CT

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

14

F

N/A

CT

Yes

1

Left frontal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

Naderzadeh et al [34]

Iran

Case report

1

12

M

Headache, nausea, vomiting, fever, decreased vision

MRI

Yes

1

Left parieto-occipital

4.56

N/A

Surgical removal

None

None

Visual deficit

Albendazole

Myopia, occasional seizure

Shafiei et al [35]

Iran

Case series

3

3

M

Headache

CT

Yes

1

Left temporo-parietal

5.83

N/A

Surgical removal

None

None

None

Albendazole, Antiepileptic

Recovered

59

F

Headache, fever

CT

Yes

1

Right parieto-occipital

8.48

N/A

Surgical removal

None

None

None

Albendazole, Antiepileptic

Recovered

53

F

Angiopathy, nausea, vomiting

CT

Yes

1

Left fronto-occipital

N/A

N/A

Surgical removal

None

Rupture of Cyst

None

Albendazole, Antiepileptic

Recurrence

Nechi et al  [36]

Tunisia

Case report

1

50

F

Seizure

CT, MRI

Yes

1

Right frontal lobe

4.97

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Ekici et al [37]

Turkey

Case report

1

12

M

Headache, vomiting, diplopia

CT

Yes

>1

Right parieto-occipital

N/A

Negative

Surgical removal [Dowling]/neuronavigation

None

None

None

Albendazole

Recovered

Bagheri et al [38]

Iran

Case report

1

18

M

Nausea,vomiting, right side hemiparesis

CT, MRI

Yes

1

Left temporal

6

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Bušić et al [39]

Croatia

Case report

1

37

F

Headache, vomiting, balance difficulties, left side hemiparesis

CT, MRI

Yes

5

Right parietal lobe

N/A

Positive

Surgical removal

None

None

Wound infection and osteomyelitis

Albendazole

Recurrence

Nashibi et al.  [40]

Iran

Case report

1

59

M

Disorientation, right side hemiparesis, headache, dysarthria

CT, MRI

Yes

1

Left parieto-temporal

N/A

N/A

Surgical removal [Dowling]

None

None

None

N/A

Improved

Ammor et al [41]

Morrocco

Case report

1

4

N/A

Weakness, headache, vomiting

Contrast MRI

Yes

1

Right fronto-temporo-parietal

N/A

N/A

Surgical removal

None

None

None

N/A

Headache, subdural hygroma

Alok et al [42]

Syria

Case report

1

5

F

Right side hemiparesis

CT, MRI

Yes

1

Pons

2.1

Positive

Surgical removal [Dowling-Orlando]

None

None

None

Albendazole

Improved

Chatzidakis et al [43]

Greece

Case report

1

27

M

Quadriparesis, headache, nausea, vomiting

CT, MRI

Yes

>1

Bilateral frontal, bilateral occipital, cerebellum

N/A

N/A

Surgical removal [3 times]

None

None

Generalized seizure post 1st OP

Albendazole

Recovered

Panagopoulos et al  [44]

Greece

Case report

1

11

M

Headache, vomiting

Contrast CT, contrast MRI

Yes

1

Right fronto-parietal

6.85

Negative

Surgical removal/neuronavigation

None

None

None

Albendazole

Improved

Karaaslan et al [45]

Turkey

Case report

1

22

M

Nausea,vomiting, headache

CT,MRI

Yes

1

Left parieto-occipital

6.92

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Hajhouji et al [46]

Morocco

Case report

1

17

F

Seizure

Contrast MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Tascu et al [47]

Romania

Case report

1

3

N/A

Post cranio-cerebral trauma

Contrast CT, MRI

Yes

1

Left fronto-parieto-occipital lobe

10

N/A

Surgical removal [Arana]

None

None

None

N/A

Subdural hematoma

Ghaemi et al [48]

Iran

Case report

1

28

M

Headache, nausea, vomiting

CT,MRI

No

1

Right temporal

6

N/A

Surgical removal

None

None

None

N/A

N/A

Ganjeifar et al [49]

Iran

Case report

1

13

M

Fever ,abdominal pain

CT, MRI

Yes

1

Left parieto-occipital

N/A

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Nemati et al [50]

Iran

Case report

1

6

M

Ataxia, left side hemiparesis

CT,MRI

Yes

1

Right fronto-parietal

13.29

Negative

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Mehrizi et al.  [51]

Iran

Case report

1

5

F

Headache, nausea, vomiting

CT

Yes

1

Fronto-parietal

10

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Fakhouri et al  [52]

Syria

Case report

1

5

F

Headache, vomiting, difficult walking

CT, MRI

Yes

1

Right Cerebellum

6

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Ghasemi et al  [53]

Iran

Case report

1

8

F

Malaise, vomiting, headache

CT, contrast MRI

Yes

1

Left temporo-parieto-occipital

N/A

Negative

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Mallik et al.  [54]

India

Case report

2

10

M

Headache, vomiting, right side hemiparesis, aphasia

MRI

Yes

1

Left temporo-parietal

10.32

N/A

Surgical removal [Dowling]

None

Rupture of Cyst

None

Albendazole, Antibiotics, Antiepileptic, Steroids

Improved

16

M

Decreased vision, headache, vomiting

CECT

Yes

1

Left fronto-temporo-parietal

N/A

Positive

Surgical removal [Dowling]

None

Rupture of Cyst

None

Albendazole

Seizure, unconsciousness

Arora et al[55]

India

Case report

1

9

F

Seizure, decreased vision, headache, vomiting

CT

Yes

1

Left parietal lobe

7.23

Positive

Surgical removal [Dowling]

None

None

None

N/A

N/A

Al-Musawi et al [56]

Iraq

Case report

1

14

F

Seizure

CT

Yes

1

Left parietal

N/A

N/A

Burr-hole surgical removal

Deterioration in the consciousness, right side hemiparesis, apnea

None

None

Albendazole, anticonvulsant

Recovered

Ghasem et ali [57]

Iran

Case report

1

30

F

Seizure, headache, intellectual impairment, abnormal behavior

CT, MRI

Yes

1

Left frontal

N/A

N/A

Surgical removal [Dowling]

None

None

None

N/A

Recovered

Polat et al. [58]

Turkey

Case report

1

45

M

Personality disorder, nausea, vomiting

CT, MRI

Yes

1

Left fronto-parietal

N/A

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

Recurrence & Death

Hmada et al [59]

Morocco

Case report

2

5

F

Decreased vision, tremor

CT

Yes

1

Right fronto-temporo-parietal

N/A

N/A

Surgical removal [Arana]

None

None

None

Albendazole, Antiepileptic

Improved

5

F

Right side heaviness

N/A

Yes

1

Right fronto-temporo-parietal

N/A

N/A

Surgical removal [Arana]

None

None

None

Albendazole, anticonvulsant

Recovered

Senapati, et al [60]

India

Case report

2

22

M

Vomiting, disorientation

CT, MRI

Yes

>1

Left parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

Cyst wall puncture

None

N/A

Recovered

40

M

Seizure, headache, vomiting, right side hemiparesis

CT

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

N/A

Recovered

Imperato et al [61]

Italy

Case report

1

9

M

Headache, diplopia

CT, MRI

Yes

1

Right temporo-parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Ramosaço et al  [62]

Albania

Case report

1

22

F

Headache, vomiting, seizure

MRI

Yes

6

Left frontal lobe, left frontal-parietal, left temporo-parietal, right occipital and right frontal

1st:2.79 2nd:4.18 3rd:4.29 4th:2.89 5th:4.09 6th:2.84

Positive

Surgical removal

None

None

None

Albendazole, Antiepileptic

Encephalomalacia

Ravanbakhsh et al [63]

Iran

Case report

1

12

M

Vision disturbance

MRI

Yes

1

Left parietal

8

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Pulavarty  [64]

India

Case report

1

16

F

Generalized seizure

CT

Yes

1

Left fronto-temporal

4.89

N/A

Surgical removal [Dowling]

None

Rupture of cyst

None

Albendazole

Recovered

Shastry et al. [65]

Iran

Case report

1

7

F

Blurred vision

CT

Yes

1

Left parieto-temporal

5.65

N/A

surgical removal [Dowling]

None

None

None

N/A

N/A

Chen et al  [66]

China

Case report

1

28

F

Seizure

MRI

Yes

1

Right frontal

N/A

Positive

Conservative [Albendazole]

N/A

N/A

N/A

None

Size of the cyst reduced

Kaushik et al [67]

India

Case report

1

53

M

Seizure exacerbation

CT

Yes

>1

Right parieto-occipital

N/A

N/A

Surgical removal

None

None

None

Albendazole

N/A

Wani, et al  [68]

India

Case report

1

13

M

Generalized seizure, vomiting

Contrast CT

Yes

1

Right occipital

8.48

N/A

Surgical removal

None

None

None

N/A

Recovered

Armanfar et al  [69]

Iran

Case report

1

46

F

Headache, blurred vision

CT, MRI

Yes

>1

Right parieto-occipital

N/A

N/A

Surgical removal

None

Rupture of cyst

None

Albendazole

Recovered

Khan et al [70]

Pakistan

Case report

1

8

M

Headache, fever, vomiting

Contrast MRI

Yes

19

Right frontal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole, Steroid, Antibiotic, Antiepileptic

Recovered

Charles et al [71]

Congo

Case report

1

32

N/A

Seizure, vomiting

Contrast CT

Yes

2

Bilateral hemisphere, right temporo-parietal

1st:1.02  2nd:6.87

N/A

Surgical removal [Arana]

None

None

None

Albendazole, Steroid

Improved

Garg et al.  [72]

India

Case report

1

47

M

Headache, vomiting

MRI

Yes

7

Both sides of cerebrum

N/A

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

Disturbed verbal output

Abuhajar et al [73]

Libya

Case report

1

50

M

Headache, left side numbness, left toes paresthesia, vomiting

Contrast CT, MRI

Yes

3

Right temporo-parietal

1st: 3.5 2nd: 3.8 3rd: 4.0

N/A

Surgical removal

N/A

N/A

N/A

N/A

N/A

Umerani et al.  [74]

Pakistan

Case report

1

22

F

Headache

CT, MRI

Yes

1

Right temporo-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Touzani et al.  [75]

Morocco

Case report

1

5

M

Vomiting , weakness, seizure

CT

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Kibzai et al [76]

Pakistan

Case series

3

10

M

Left side paresthesia, nausea

CT, contrast MRI

Yes

1

Right temporo-parietal

N/A

N/A

Surgical removal [Dowling]

None

Puncture of Cyst

None

Albendazole, Antiepileptic

Recurrence

40

M

Vomiting, altered behavior

CT, MRI

Yes

1

Left parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

Rupture of cyst

None

Albendazole

Recovered

72

M

Seizure, personality disorder

CT, MRI

Yes

32

Right frontal

N/A

N/A

Surgical removal

None

None

None

Albendazole

Improved

Duransoy et al [77]

Turkey

Case report

1

13

M

Headache, nausea, vomiting

CT

Yes

1

Right temporo-parietal

10

N/A

Surgical removal [Arana]

None

None

Left hemiparesis, subdural hygroma

Albendazole

Improved

Qureshi et al [78]

Pakistan

Case report

1

11

M

Seizure

MRI

Yes

1

Left posterior-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

N/A

N/A

Senol et al.  [79]

Turkey

Case report

1

6

F

Headache with photophobia and phonophobia

MRI

Yes

1

Right frontotemporal

10.5

Negative

Surgical removal [Dowling]

None

None

None

Albendazole, Antiepileptic

Recovered

Kandemirli et al [80]

Turkey

Case report

1

6

M

Nausea, vomiting

CT

Yes

1

Right frontal extended to lateral ventricle

7.95

N/A

Surgical removal [Dowling]

None

None

None

Albendazole, Antiepileptic

Recovered

Bahannanet al [81]

Yemen

Case report

1

17

M

Imbalance, ataxia, falls, right side hemiparesis, fever, headache, decreased visual acuity, diplopia.

CT

Yes

1

Right fronto-parietal

5

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Kumar et al [82]

India

Case report

1

25

M

Headache, vomiting, right side weakness, seizure

Contrast CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal

None

None

None

N/A

N/A

Agrawal et al [83]

India

Case report

1

25

M

Difficulty walking, seizure

CT, contrast MRI

Yes

1

Left fronto-parietal

24.63

N/A

Surgical removal

None

None

None

Albendazole

N/A

Mustafa et al  [84]

Iraq

Case report

1

2

M

Focal seizure

CT

Yes

1

Left parietal

6

N/A

Surgical removal [Dowling]

None

None

None

none

Recovered

IJaz et al [85]

Pakistan

Case report

1

8

M

Headache, fever, right-side hemiparesis, difficult walking

CT

Yes

1

Left cerebrum

8.94

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Borni et al [86]

Tunisia

Case report

1

5

M

Headache, vomiting

CT, contrast MRI

Yes

2

Left occipital

1st: 3.39 2nd: 2.25

Positive

Surgical removal

None

Puncture of Cyst

None

Albendazole

Recovered

Kojundzicet al [87]

Croatia

Case report

1

34

F

Headache, vomiting

CT, MRI

Yes

3

Right temporo-parietal

1st:3.8 2nd:2.9 3rd: N/A

Positive

Surgical removal

None

None

Osteomyelitis

Albendazole

Improved

Siyadatpanah et al [88]

USA

Case report

1

39

M

Right side paresthesia, imbalance

MRI

Yes

1

Left fronto-parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

Akrim et al [89]

Morocco

Case report

1

22

F

Headache, vomiting, blurred vision

CT

Yes

>1

Left parieto-occipital

N/A

N/A

Surgical removal [Arana]

None

None

Neurological deficit

Albendazole

Improved

Zeynal et al [90]

Turkey

Retrospective cohort

12

50

M

Headache, left side hemiparesis

CT, MRI

Yes

1

Right parietal

N/A

N/A

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 4

55

M

Dysarthria, focal seizure

CT, MRI

Yes

1

Left temporo-parietal

N/A

N/A

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

40

M

Headache, nausea, vomiting

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 4

26

M

Headache, left side hemiparesis

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

35

F

Headache, right side hemiparesis

CT, MRI

Yes

1

Left thalamus

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

25

M

Right side hemiparesis

CT, MRI

Yes

1

Left thalamus

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 4

64

M

Dysphasia

CT, MRI

Yes

1

Right temporal

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Death

27

F

Headache, nausea, vomiting, altered consciousness

CT, MRI

Yes

1

Left parietal

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

13

M

Right side hemiparesis

CT, MRI

Yes

1

Left parieto-occipital

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

62

M

Left side hemiparesis

CT, MRI

Yes

1

Right fronto-parietal

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Death

49

M

Headache

CT, MRI

Yes

1

Right parieto-occipital

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

52

M

Headache

CT, MRI

Yes

2

Left temporal, right frontal

N/A

Positive

Surgical removal

N/A

N/A

N/A

Albendazole

Glasgow outcome: 5

Ozdol et al [91]

Croatia

Case report

1

23

M

Nausea, imbalance, headache, urinary and fecal incontinence

MRI

No

1

Left cerebellum

2.08

Positive

Surgical removal

None

None

None

Albendazole

Recovered

Ma et al  [92]

China

Case report

2

50

M

Headache, nausea, vomiting

Contrast CT, contrast MRI

Yes

2

Right frontal, left temporal

N/A

N/A

Surgical removal

None

None

None

Albendazole

Recovered

42

F

Headache, vomiting

Contrast CT, contrast MRI

Yes

2

Left frontal, left temporal

N/A

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Mokhtari et al [93]

Iran

Case report

1

60

F

Headache, bilateral decreased vision, delusions, cognitive disorders

Contrast CT, MRI

Yes

2

Left fronto-parietal, right parieto-occipital

1st: 3 2nd: 2.08

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Benzagmout et al [94]

Morrocco

Case report

2

21

F

Seizure

Contrast CT, contrast MRI

Yes

1

Right frontal

N/A

N/A

Surgical removal

None

None

None

Antiepileptic

Recovered

24

F

Headache, vomiting

CT

No

1

Right frontal

4.47

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Ray et al [95]

India

Case report

1

4

M

Headache, nausea, vomiting, altered sensorium, fever

CT

Yes

>1

Left fronto-parietal

N/A

Negative

Surgical removal [ Dowling]

N/A

N/A

Meningitis, subdural effusion, hydrocephalus

N/A

Recovered

Yiş et al  [96]

Turkey

Case report

1

7

M

Headache, vomiting, myalgia, abdominal pain

MRI

Yes

1

Temporo-parieto-occipital

8

N/A

Surgical removal [ Dowling]

None

None

None

Mebendazole

Recovered

Per et al  [97]

Turkey

Case series

5

15

M

Headache, intellectual impairment, dysphasia

CT

Yes

4

Left fronto-parietal , left occipital

N/A

N/A

Surgical removal [ Dowling]

None

None

None

N/A

Recurrence & Death

15

M

Headache, faintness, diplopia, vomiting

CT, MRI

Yes

1

Right temporo-parietal

N/A

N/A

Surgical removal [ Dowling]

None

None

None

Albendazole

Recovered

4

F

Headache, nausea, vomiting, seizure

CT

Yes

1

Right parietal

N/A

N/A

Surgical removal [ Dowling]

None

None

None

Albendazole

Recurrence

16

M

Vomiting , seizure, headache

MRI

Yes

1

Right parietal

N/A

N/A

Surgical removal [ Dowling]

None

None

None

Albendazole

Recovered

11

M

Headache, vomiting, strabismus

MRI

Yes

>1

Right occipital,right parietal

N/A

N/A

Surgical removal [ Dowling]/neuronavigation

None

None

None

N/A

Improved

Radmenesh et al [98]

Iran

Case report

2

7

F

Headache,vomiting, right side hemiparesis

CT

Yes

4

Left frontal

N/A

Negative

Surgical removal

None

None

Hydrocephalus

Albendazole

Recovered

12

M

Headache,vomiting

CT

Yes

1

Right fronto-temporal

N/A

Negative

Surgical removal

None

None

None

Albendazole

Recovered

Balak et al  [99]

Turkey

Case report

1

16

M

Headache, visual disturbance

CT, MRI

Yes

1

Right parieto-occipital

6

Positive

Surgical removal/microsurgery

None

None

None

Albendazole

Recovered

Najjar et al  [100]

Saudi Arabia

Case report

1

11

M

Left side hemiparesis

CT, contrast MRI

Yes

1

Right hemisphere

8

Negative

Burr-hole surgical removal

None

Puncture of Cyst

Abscess at surgical site

Albendazole

Recovered

Tatli et al [101]

Turkey

Case report

3

7

M

Headache, left side hypoesthesia

CT, MRI

Yes

1

Right parietal

7.65

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Recovered

15

F

Headache, vomiting

CT

Yes

1

Left fronto-parietal

8.48

N/A

Surgical removal [Dowling]

None

Rupture of cyst

None

Albendazole

Recovered

10

F

Headache, vomiting, left side weakness

CT, MRI

Yes

1

Right fronto-temporo-parieto-occipital

10.32

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

N/A

Yurt et al  [102]

Turkey

Case report

1

19

F

Headache, vomiting, seizure

CT, MRI

Yes

>1

Bilateral hemispheres

N/A

Negative

Multiple surgeries

Left side hemiplegia, deterioration

None

Recurrence of symptoms

Albendazole

Recurrence

Aydin et al[103]

Turkey

Case report

1

7

M

Headache,behavioral disturbance, counting and calculation disorders, mental regression

CT

Yes

1

Left temporo-parietal

7.48

Positive

Surgical removal

None

None

Left hemiparesis

Mebendazole

Recovered

Tuzun et al [104]

Turkey

Case series

13

9

M

Headache, seizure

CT, MRI

Yes

1

Left parieto-occipital

N/A

N/A

Surgical removal [Dowling]

Deterioration

None

Subdural effusion

Albendazole

Improved

5

M

Right side hemiparesis

CT, MRI

Yes

1

Left parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

Porencephalic cyst

Albendazole

Improved

16

F

Headache, nausea, vomiting

CT, MRI

Yes

1

Right parieto-occipital

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

11

F

Headache, nausea, vomiting

CT, MRI

Yes

1

Left temporo-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

Cerebral spinal fluid collection

Albendazole

Improved

12

M

Left side hemiparesis, seizure

CT, MRI

Yes

1

Right frontal

N/A

N/A

Surgical removal [Dowling]

Deterioration

None

Subdural effusion

Albendazole

Improved

8

F

Headache, loss of consciousness

CT, MRI

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal [Dowling]

Deterioration

None

None

Albendazole

Improved

3

M

Right side hemiparesis

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

Deterioration

None

Subdural effusion

Albendazole

Improved

17

M

Headache, left side hemiparesis

CT, MRI

Yes

1

Right parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

18

M

Headache, right side hemiparesis

CT, MRI

Yes

1

Left fronto-parietal

N/A

N/A

Surgical removal [Dowling]

None

None

Hemorrhage

Albendazole

Improved

16

F

Right side hemiparesis

CT, MRI

Yes

>1

Left occipital, left parietal

N/A

N/A

Surgical removal [Dowling]

None

Rupture of cyst

None

Albendazole

Recurrence

11

M

Headache

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

9

F

Headache, nausea, vomiting

CT, MRI

Yes

1

Right occipital

N/A

N/A

Surgical removal [Dowling]

None

None

Hemorrhage

Albendazole

Improved

5

F

Headache, right side hemiparesis

CT, MRI

Yes

1

Left parietal

N/A

N/A

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Bakaris et al  [105]

Turkey

Case report

1

8

F

Right upper paresis, headache

CT

Yes

1

Left temporo-parieto-occipital

8.14

N/A

Surgical removal

None

None

None

Albendazole

Recovered

Guney et al  [106]

Turkey

Case report

1

18

M

Headache, neck pain

CT

Yes

1

Left fronto-parietal

N/A

Positive

Surgical removal

None

None

None

N/A

N/A

Önal et al  [107]

Turkey

Case report

1

7

F

Ataxia, apraxia, Headache, tremor

CT, MRI

Yes

1

Right temporo-parietal

6.21

N/A

Surgical removal [Dowling]

None

None

None

N/A

Recovered

Muthusubramanian et al  [108]

India

Case report

1

40

F

Headache, right side hemiparesis, double vision, gait abnormality

Contrast CT

Yes

1

Pons

N/A

N/A

Surgical removal

None

None

None

N/A

Improved

Kabatas et al  [109]

Turkey

Case report

1

26

F

Headache, nausea, vomiting, seizure

MRI

Yes

1

Left frontal

4.13

Positive

Surgical removal [Dowling]

None

None

None

Albendazole

Improved

Menkü et al [110]

Turkey

Case report

1

35

M

Seizure

CT, MRI

No

1

Righ parieto-occipital

4.74

Negative

Surgical removal

None

None

None

N/A

Recovered

Anvari et al [111]

Iran

Case report

1

5

F

Headache, nausea, vomiting

Contrast CT

No

1

Right fronto-parietal

N/A

N/A

Burr-hole surgical removal

None

None

None

Albendazole

Recovered

Karadag˘et al [112]

Turkey

Case report

1

45

F

Seizure, confusion

CT

Yes

2

Left fronto-parietal, right parietal

5

Negative

Surgical removal

Deterioration

Puncture of the left cyst

None

Albendazole

Recurrence

CT; computed tomography, MRI; magnetic resonance imaging, ISHC; Imaging suggested hydatid cyst, N/A; non-available, OP; operative, *Improved = Symptomatic improvement but not complete recovery during the follow-up period. Recovered = Complete recovery/free of symptoms.

Table 2. Baseline characteristics of the study and the participants.

Variables	Frequency/Percentage
Country of study    Turkey    Iran    India    Morocco    Iraq    Pakistan    Croatia    Others	27 (24.1%) 19 (16.7%) 17 (15.2%) 11 (9.8%) 5 (4.6%) 5 (4.6%) 3 (2.7%) 25 (22.3%)
Study design    Case Report    Case Series    Retrospective cohort	101 (90.2%) 10 (8.9%)                                          1 (0.9%)
Age, year, mean [SD]	20.44± 16.76
Age group    ≤9    10-19    20-29    30-39    40-49                                          50-59    60-69    70-79    80-89	52 (29.2%) 62 (34.8%) 24 (13.5%) 12 (6.7%) 12 (6.7%) 10 (5.6%) 3 (1.7%) 1 (0.6%) 2 (1.1%)
Gender    Male    Female    N/A	107 (60.1%) 68 (38.2%) 3 (1.7%)
Residency    Rural    Urban    N/A	71 (39.9%) 8 (4.5%) 99 (55.6%)
Previous history of hydatid disease    Yes    No    N/A	13 (7.3%) 161 (90.5%) 4 (2.2%)
Type of hydatid disease    Cystic    Alveolar	158 (88.8%) 20 (11.2%)
Presentation    Symptomatic    Asymptomatic	168 (94.4%) 10 (5.6%)
Presenting complaint Headache Vomiting Nausea Seizure Paresis Impaired vision Impaired conscious level Speech abnormalities * Fever Altered sensorium ** Psychological disturbance Other symptoms	112 (62.9%) 77 (43.3%) 35 (19.7%) 54 (30.3%) 51 (28.7%) 23 (13%) 12 (6.7%) 10 (5.6%) 8 (4.5%) 8 (4.5%) 7 (4.0%) 31 (17.4%)
Duration of presenting symptoms [mean]	19 weeks
Multiple organ involvement    Yes    No    N/A	48 (27%) 128 (71.9%) 2 (1.1%)
Site of the cyst/lesion [s]    Left-side multi-lobe involvement    Right-side multi-lobe involvement    Bilateral multi-lobe involvement    Frontal lobe    Parietal lobe    Temporal lobe    Occipital lobe    Left Hemisphere [unspecified location]    Right Hemisphere [unspecified location]    Other [Cerebellum, Thalamus, Pons]	50 (28.1%) 47 (26.4%) 11 (6.2%) 17 (9.6%) 33 (18.5%) 5 (2.8%) 4 (2.2%) 2 (1.1%) 2 (1.1%) 7 (4%)
Disease status per number of cysts/lesions    Primary-solitary    Primary-multiple    Secondary-solitary    Secondary-multiple	118 (66.3%) 27 (15.1%) 23 (13%) 10 (5.6%)
Neurological+/-other physical examination    Normal    Positive findings    N/A	30 (16.8%) 92 (51.7%) 56 (31.5%)
CT/MRI Findings    Suggesting hydatid disease    Not suggesting hydatid disease	170 (95.5%) 8 (4.5%)
Serology    Positive Negative    N/A	34 (19.1%) 21 (11.8%) 123 (69.1%)
Type of management Conservative Surgical/Open *** Burr-hole	5 (2.8%) 170 (95.5%) 3 (1.7%)
Disease outcome Death Survived N/A	6 (3.4%) 139 (78.1%) 33 (18.5%)
Recurrence    Recurrence alive    Recurrence dead	11 (6.2%) 2 (1.1%)
* Speech abnormalities: aphasia, apraxia of speech, dysphonia, slurred speech, and others.  **Altered sensorium: paresthesia, numbness, and heaviness. *** Surgical removal by (Dowling technique, modified Arana-Inguinz technique, surgical removal under neuronavigation, and microsurgery).

Discussion

The World Health Organization (WHO) has categorized human echinococcosis under the umbrella of tropical neglected diseases (TNDs) that require control, as the disease remains a significant health issue in endemic regions [1]. 

Domestic dogs serve as the primary definitive hosts for both species of Echinococcus and pose the highest risk of transmitting cystic and alveolar echinococcosis to humans. Infection in dogs occurs when they consume livestock offal containing hydatid cysts, after which they release parasite eggs in their feces, contaminating soil, water, and grazing fields. Livestock acquire the infection by ingesting these eggs during grazing, while humans are most often infected through eating or drinking contaminated food or water [114,115].

In this systematic review, studies on two genera of clinical interest, Echinococcus granulosus and Echinococcus multilocularis, have been reviewed. Several mechanisms have been proposed for the migration of Echinococcus larvae to the brain. Larvae hatching from ingested eggs in the intestine enter the portal circulation, spreading to different tissues where they develop hydatid disease. Two barriers can protect against CNS involvement: the first is the liver through portal circulation, and the second is the lung, which may act as a secondary filter. The lack of these effective sieves, problems in the immune system, special architecture of brain tissue, disrupted capillaries in the lungs, and structural heart diseases such as patent ductus arteriosus and patent foramen ovale may all provide a gateway to the brain [10,11]. This disease commonly affects supratentorial regions of the brain, specifically within the distribution of the middle cerebral artery, primarily targeting the parietal and frontal lobes [77,78,107]. Generally, BHD is classified as “primary” or “secondary”. The primary disease is rare; it results from direct infestation of the brain without the involvement of other organs. It most often presents as a solitary, spherical, and unilocular cyst surrounded by a broad capsule, which usually contains protoscoleces and renders a fertile lesion. The secondary type is typically characterized by multiple cerebral cysts that result from the rupture of a cyst in other organs. They lack brood capsules and protoscoleces, rendering them infertile. Therefore, the risk of recurrence after their rupture is negligible. However, on rare occasions, multiple primary cysts can occur within the brain parenchyma due to multiple larval intakes in patients with defective immune systems, metastatic deposits from the rupture of a primary cyst in the brain, or the presence of cardiac anomalies. On the other hand, alveolar disease tends to result in multiple intracerebral lesions and might resemble and behave as a malignant lesion [90-93]. Cerebral HD is considered a childhood disease, most commonly (50–75%) seen in children and young adults. Additionally, patients with cerebral HDs may also have concomitant cysts in other organs, although this occurs in less than 20% of patients with intraparenchymal hydatidosis [5,6,105].

 In this systematic review, most of the cases (64%) were affected during their first and second decades of life. Multiple cysts or lesions were present in about 21% of the cases. Among these, 15.1% were primary multiple diseases, while only 5.6% of the cases had secondary multiple hydatidosis. Thus, the findings of this review disagree with the assumption that primary multiple BHD is rarer than secondary multiple lesions. Additionally, 48 cases (27%) had concomitant disease in other organs.

Signs of raised intracranial pressure (headache, nausea, vomiting) and focal neurological deficits are the most common presentations of the disease. Seizures, visual disturbances, and cranial nerve involvement are also common presenting complaints reported in the literature [103,104]. In this study, headache was the most common presenting symptom (62.9%), followed by vomiting (43.3%), similar to the other reported studies. Seizure, paresis, nausea, and visual disturbance were reported in 30.3%, 28.7%, 19.7%, and 13% of the cases, respectively. The mean duration of symptoms at the time of presentation was 19 weeks.

Timely diagnosis of BHDs is crucial because failure to make a prompt diagnosis could result in fatal consequences. Moreover, handling the cystic or mass lesion during surgical intervention is essential for reducing intraoperative complications and preventing disease recurrence. It has been declared that serological testing for the diagnosis of HD is of limited accuracy. Therefore, it is not sufficient on its own to confirm the diagnosis of HD [104]. Imaging modalities are the mainstay of diagnosis in patients with suggestive history and clinical findings, even when serological tests are negative. The disease generally poses common characteristics and pathognomonic features on scanners. Typically, CT and MRI are the primary imaging techniques, which can often be sufficient to achieve a diagnosis. For BHD, the main appearance on CT is a round, intra-parenchymal, usually large cystic lesion with a well-defined border. The cyst fluid is typically isodense or slightly hyperdense compared to cerebrospinal fluid. Calcifications or septations may or may not be present. Calcifications are primarily peri-cystic, giving a 'ground-glass' appearance, suggesting infection or damage before the larva's death. The MRI scans show a thin-walled spherical cyst containing fluid with cerebrospinal fluid characteristics on all sequences. Rim wall contrast enhancement and peripheral edema are much less common in hydatid cysts, and when present, may suggest other radiological differential diagnoses. The presence of multiple small daughter endocysts, characteristic of cystic echinococcosis, is the key distinguishing feature from other cystic lesions in the brain [1-4]. There are a few reports on the CT and MRI appearance of cerebral AE. The lesions may appear as solid, semisolid, or lobulated cystic or mass lesions with definite margins. Calcifications are usually scattered throughout the lesion, unlike in CE, where they are mainly confined to the pericystic region. Predominant features include surrounding edema and various types of contrast enhancement, such as peripheral ring-like, heterogeneous, nodular, and cauliflower-like patterns, indicating an inflammatory reaction around the lesion. Diffusion-weighted MRI is useful in distinguishing lesions from edema. Therefore, the diagnosis should be based on evidence of a primary focus in another location, an appropriate clinical history, the prevalence of the infection in the host's geographic location, and laboratory findings, as a standard practice for diagnosing and differentiating cerebral AE [90-94]. Following laboratory tests and imaging, a histopathological examination confirms the final diagnosis [80,97]. Regarding the findings of this systematic review, a serology test was performed in 30.9% of the studies, and it was positive in 19.1% of the cases. Although this study could not statistically confirm the exact role of serology in detecting BHD, the data suggest that serology alone cannot be relied upon for diagnosing cerebral HD. Additionally, imaging modalities, including both CT and MRI, were indicated for the diagnosis of the disease in 95.5% of cases.  The management of BHD typically involves a combination of surgical and adjunctive medical therapies. The treatment plan may vary depending on the size, number, location, and depth of invasion of the lesions into the brain parenchyma. Consequently, the prognosis of the disease can vary based on these factors. The most effective method is surgery. Although different surgical techniques have been investigated, there is consensus that intact cyst removal and total resection of the mass lesion without rupturing it or spilling its contents should be the core of the surgery. This approach is crucial in preventing perioperative complications, recurrence, and progression of the disease. The Dowling-Orlando technique, later modified by Arana-Iniguez and San Julian, is the most widely used surgical method for removing CNS hydatid cysts. This technique involves the formation of a hydrostatic assistant and continuous irrigation with hypertonic saline to dissect the cyst wall from the brain parenchyma, thereby achieving the intact removal of the cyst [26,42,53]. The location of the cyst, its size, adhesion to surrounding structures, multiplicity, and the presence of deep-seated lesions, especially in cases of alveolar E. multilocularis, can make the removal of the cyst intact challenging. The Dowling-Orlando technique may not be feasible in all cases of brain HD. In such situations, alternative methods aimed at minimizing the spillage of the cyst contents can be considered. The PAIR technique, which involves puncture and needle aspiration of the cyst, followed by the injection of a scolicidal solution for 20-30 minutes and cyst re-aspiration, has been reported as a reasonable approach [74,75,111].

Furthermore, the technique of burr-hole opening over the site of the cyst and the introduction of a cannula through the brain to drain the cyst, followed by removal of the cyst wall, has also been reported. However, this method of aspiration is discouraged unless total removal by other techniques is impossible. In patients with brain AE, radical excision should be performed for all accessible lesions. These procedures can be combined with the use of microsurgical and neuronavigation modalities to reduce perioperative complications [56,104]. Intraoperative cyst rupture is a common and serious event. Spillage of the cyst content into the brain tissue may lead to a fatal anaphylactic reaction, which is a chief cause of mortality during surgery. Furthermore, it increases the risk of high recurrence rates of the disease, particularly if the cyst is primary, as it is a fertile lesion [33,35]. The main reported early post-operative complications often arise due to the space left after the excision of large lesions. These may include subdural hematomas, hyperpyrexia, cerebral edema, cortical collapse, or even cardiorespiratory failure. Late post-operative complications such as porencephalic cyst, hydrocephalus, pneumocephalus, hemorrhage, seizures, and focal neurological deficits can occur in the days following surgery. These complications may require conservative management or further intervention [11,20,33]. Although the principal treatment of HD is surgery, pre-and post-operative adjunctive anthelmintic therapy, mainly with albendazole, may be considered. Albendazole can sterilize the cysts, decrease the tension in the cyst wall (thus reducing the risk of spillage during surgery and subsequently the risk of anaphylaxis and recurrence), and is also used for inoperable lesions. The optimal duration of treatment is still unclear, but recommended regimens involve albendazole taken orally at 10–15 mg/kg/day for 3–6 months, followed by a 'rest period' of 15 days after each month. Supportive medications can also be used to manage the presenting symptoms associated with the disease [12,93]. Among the several reviewed studies, a history of traumatic cyst rupture or iatrogenic cyst puncture during surgical procedures played a role in causing the recurrence of the disease [14,76,97]. In the present study, the primary treatment was surgical intervention in most cases (97.2%). The surgical approaches were commonly Dowling-Orlando or modified Arana-Iniguez (95.5%), while three cases (1.7%) underwent burr-hole surgery. In addition, five cases (2.8%) had been managed with conservative treatment only. The recurrence was reported in 13 cases (7.3%). Among them, six cases had intraoperative rupture of the cyst, and two had iatrogenic puncture of the cyst. No alveolar cases showed a recurrence. For this reason, this study recommends surgical intervention over conservative treatment. Follow-up for up to two years is recommended, especially in cases of giant hydatid disease or perioperative complications. In this systematic review, the mean follow-up period was 12 months. It has been reported that the majority of BHD cases can recover and survive with proper management [11,20]. Accordingly, the mortality rate in this study was only 3.4%. The major limitation of this study is the predominantly descriptive nature of the included studies, which may not yield reliable outcomes and can introduce bias. Further research employing rigorous study designs, such as trials comparing different surgical techniques for managing BHD, is recommended, particularly for the alveolar form.

Conclusion

Imaging modalities, such as CT and MRI, are the primary diagnostic tools for intra-parenchymal BHD, while serological tests alone are not reliable. Surgical intervention remains the definitive treatment for BHD. However, clinical diagnosis and treatment of AE continue to pose significant challenges. Therefore, in endemic regions, early diagnosis and treatment are crucial for improving prognosis. A history of cyst rupture during surgery may increase the risk of recurrence, necessitating extensive follow-up.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: Not applicable.

Patient consent (participation and publication): Not applicable.

Funding: The present study received no financial support.

Acknowledgements: None to be declared.

Authors' contributions: FHF and ASH were significant contributors to the conception of the study and the literature search for related studies. HOA and ABL involved in the literature review, study design, and manuscript writing. ZOKA, KAA, RJR, AKG, SMA, and ADA were involved in the literature review, the study's design, the critical revision of the manuscript, and data collection. FHF and HOA confirm the authenticity of all the raw data. All authors approved the final version of the manuscript.

Use of AI: ChatGPT-4.0 was used to assist in language editing and improving the clarity of the manuscript. All content was reviewed and verified by the authors. Authors are fully responsible for the entire content of their manuscript.

Data availability statement: Not applicable.