Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan.

Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP-related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C>T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C>T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.

Solitary tuberculous brain lesions: 24 new cases and a review of the literature.

A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a glioma, metastasis or other infectious disease, especially from a pyogenic brain abscess. We analyzed the clinical characteristics, diagnostic procedures and outcomes of 24 patients with STBL diagnosed in three centers from France, India and Mexico. We also reviewed 92 STBL cases previously reported in the literature. General symptoms were found in 54% of our patients, including enlarged lymph nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were hypointense on T1-weighted sequences, while T2-weighted sequences showed both a peripheral hypersignal and a central hyposignal. The diagnosis was documented microbiologically or supported histologically in 71% of cases. Clinical outcome was good in 83% of cases.

Anticardiolipin antibodies in stroke patients in Sudan. Appraisal of their significance in a region of high burden of endemic infections.

OBJECTIVE: To screen and evaluate the significance of anticardiolipin seroprevalence in patients with acute ischemic stroke, in patients with infectious disease, and in healthy subjects resident in Sudan, a tropical country endemic for several infectious diseases. METHODS: We conducted the study in Khartoum Teaching Hospital in Khartoum, Sudan between July 2003 and January 2005. We included 89 stroke cases, 30 infectious disease patients, and 30 asymptomatic healthy subjects. We estimated IgG and IgM anticardiolipin antibody titers in serum samples from all subjects in the 3 study categories at the time of hospital admission. RESULTS: We found a significantly higher prevalence of anticardiolipin antibodies in the stroke and infection groups compared to the healthy subjects. However, there was no significant difference in anticardiolipin seroprevalence between patients with stroke and patients with infectious disease. CONCLUSION: Caution is necessary when interpreting the presence of antiphospholipid antibodies as a stroke risk in patients harboring infection or living in places with high endemicity of infectious diseases.

Parasite diversity in adult patients with cerebral malaria: a hospital-based, case-control study.

Thirty adult patients with cerebral malaria (CM) were recruited for this study. Two clinical groups were used as controls: those with mild malaria (n = 20) and asymptomatic volunteers (n = 20). Thick and thin blood smears were examined for detection of Plasmodium falciparum and estimating infection intensity. A nested polymerase chain reaction (PCR) using allele-specific primers for merozoite surface protein gene was used to determine the parasite diversity of Plasmodium falciparum causing CM. Plasmodium falciparum was detected in blood smears of all malaria patients. No significant difference in parasite count was found between the groups. Thirteen (65%) of the asymptomatic volunteers had a positive PCR for P. falciparum. Multiple alleles were found in 17 (58.6%) patients with CM, but only in 7 (35.6%) with uncomplicated malaria. Multiple alleles were also found in 6 (46.2%) of the 13 PCR-positive asymptomatic individuals. We could not identify a specific strain or strains of P. falciparum that showed a significant association with disease severity. Therefore, we assume that the development of CM in adults residing in endemic areas is more dependent on strain multiplicity rather than on a specific strain or strains of P. falciparum, and that the parasite intensity has no relationship with disease severity. Asymptomatic adults may repeatedly be exposed to low levels of a wide range of different strains during low transmission season and acquire sub-patent parasitemia. This may also confer premunition that renders them relatively resistant to CM.

Guillain-Barré syndrome following acute falciparum malaria.

Plasmodium falciparum malaria is often complicated by involvement of the gastrointestinal, cardiovascular, and nervous systems. The development of Guillain-Barré syndrome in 10 patients who had had acute P. falciparum malaria during its seasonal exacerbation is reported.

Acute stroke type, risk factors, and early outcome in a developing country: a view from Sudan using a hospital-based sample.

This hospital-based prospective study was conducted to determine stroke type, risk factors, and early outcome in patients admitted with acute stroke in both Khartoum and Shaab hospitals located in the capital city of Sudan. Consecutive stroke patients presenting within 48 hours of onset were included in the study. Data were obtained from history taking, physical examination, and investigations. Cranial computed tomography (CT) scanning was performed on 18 patients. The diagnosis of stroke type in patients who did not have CT examination was determined by clinical criteria. Ninety-six patients, 56 males and 40 females, were studied. The peak age group was 61 to 80 years. Stroke caused by infarction was found in 58.3% while stroke caused by hemorrhage was found in 41.6%. Hypertension was the most common associated risk factor, constituting 46.9%. Cardiac disease was found in 16%, diabetes mellitus in 14.6%, syphilis in 4.1%, and previous transient ischemic attack in 2.1%. The overall mortality was higher than in western countries. Risk factors for stroke in Sudan are the same as elsewhere; however, the peak age group is one decade earlier than in developed countries. In developing countries, promoting hypertension and acute stroke health care programs are essential to cutting morbidity and mortality rates.

Autosomal dominant cerebellar ataxia type 1 in a Sudanese family.

OBJECTIVE: To study a large Sudanese family with a progressive autosomal dominant cerebellar ataxia and describe the clinical features and identify the genotype of the disorder. METHODS: This study was conducted during the year 1999 in the University Neurology Department of Shaab Teaching Hospital in Khartoum, Sudan. Affected individuals were identified by clinical examination or by reliable narrative data obtained from relatives of diseased or inaccessible family members. Routine laboratory blood and urine tests, cerebrospinal fluid analysis, cranial computerized tomography and nerve conduction studies were performed on the index patient and, if possible, family members. The genotype was identified by deoxyribonucleic acid analysis. RESULTS: Ten males and 12 females spanning 4 generations were affected by autosomal dominant spinocerebellar ataxia. Genetic studies identified the mutation to be at the spinocerebellar ataxia 1 locus on chromosome p6. CONCLUSION: This is a report of a Sudanese family suffering from Type 1 autosomal dominant spinocerebellar ataxia.