Noshir Wadia

A proposal to declare neurocysticercosis an international reportable disease

Neurocysticercosis is an infection of the nervous system caused by Taenia solium. It is the most important human parasitic neurological disease and a common cause of epilepsy in Africa, Asia, and Latin America, representing enormous costs for anticonvulsants, medical resources and lost production. Neurocysticercosis is a human-to-human infection, acquired by the faecal-enteric route from carriers of intestinal T. solium, most often in areas with deficient sanitation. Intestinal tapeworms cause few symptoms, but adult taeniae carried by humans release large numbers of infective eggs and are extremely contagious. Ingestion of poorly cooked pig meat infested with T. solium larvae results in intestinal taeniosis but not neurocysticercosis. With a view to hastening the control of taeniosis and neurocysticercosis we propose that neurocysticercosis be declared an international reportable disease. New cases of neurocysticercosis should be reported by physicians or hospital administrators to their health ministries. An epidemiological intervention could then be launched to interrupt the chain of transmission by: (1) searching for, treating and reporting the sources of contagion, i.e. human carriers of tapeworms; (2) identifying and treating other exposed contacts; (3) providing health education on parasite transmission and improvement of hygiene and sanitary conditions; and (4) enforcing meat inspection policies and limiting the animal reservoir by treatment of pigs. We believe that the first step required to solve the problem of neurocysticercosis is to implement appropriate surveillance mechanisms under the responsibility of ministries of health. Compulsory notification also has the major advantage of providing accurate quantification of the incidence and prevalence of neurocysticercosis at regional level, thus permitting the rational use of resources in eradication campaigns.

Proposal of diagnostic criteria for human cysticercosis and neurocysticercosis

Taenia solium cysticercosis is a major public health problem in several areas of the world. While the disease has a recognized etiologic agent, its definitive histological diagnosis is not possible in most cases because this parasite tends to lodge in cerebral tissues where routine biopsy is not feasible. Therefore, the diagnosis of human cysticercosis (and neurocysticercosis) should rest on the proper interpretation of the patients symptoms together with data provided by radiological studies and immunologic tests for the detection of anticysticercal antibodies. Unfortunately, the pleomorphism of this parasitic disease creates confusion when non-specific clinical, radiological, or immunologic criteria alone are used to detect cases among populations or to diagnose hospitalized patients with neurological manifestations. We propose a chart of diagnostic criteria for human cysticercosis that objectively permit clinicians and health care workers to evaluate clinical, radiological, immunologic, and epidemiologic data of patients. The chart uses four degrees of criteria: absolute, major, minor, and epidemiologic, that were selected on the basis of their individual diagnostic strength. Interpretation of such criteria will result in three categories of diagnostic certainty: definitive, probable and possible, according to the likelihood that cysticercosis is present in a given person.

Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: A report on three patients

We describe three patients who developed a rapidly evolving posttraumatic akinetic‐rigid syndrome (ARS), the clinical manifestations of which were similar to Parkinsons disease, including response to levodopa. Despite initial imaging studies showing traumatic damage to the substantia nigra, the ARS appeared after a delay of 1–5 months after the injury. We stress the importance of magnetic resonance imaging to illustrate nigral damage in all patients in whom head trauma precedes an ARS.

A common disease haplotype segregating in spinocerebellar ataxia 2 (SCA2) pedigrees of diverse ethnic origin.

The identification of a CAG trinucleotide repeat expansion, located within the coding sequence of the ataxin-2 gene, as the mutation underlying spinocerebellar ataxiaxa02 (SCA2) has facilitated direct investigation of pedigrees previously excluded from linkage analysis due to insufficient size or pedigree structure. We have previously described the identification of the ancestral disease haplotype segregating in the Cuban founder population used to assign the disease locus to chromosome 12q23–24.1. We now report evidence for the segregation of the identical core haplotype in pedigrees of diverse ethnic origin from India, Japan and England, established by the analysis of the loci D12S1672 and D12S1333 located 20xa0kb proximal and 200xa0kb distal to the triplet repeat motif respectively. Interpretation of this data is suggestive that for these pedigrees at least, the mutation has arisen on a single ancestral or predisposing chromosome.

Pure Cerebellar Ataxia with Homozygous Mutations in the PNPLA6 Gene

Autosomal-recessive cerebellar ataxias (ARCA) are clinically and genetically heterogeneous conditions primarily affecting the cerebellum. Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations in a field where the genotype-phenotype correlations are rapidly expanding. We identified two cousins from a consanguineous family belonging to a large Zoroastrian (Parsi) family residing in Mumbai, India, who presented with pure cerebellar ataxia without chorioretinal dystrophy or hypogonadotropic hypogonadism. We used a combined approach of clinical characterisation, homozygosity mapping, whole-exome and Sanger sequencing to identify the genetic defect in this family. The phenotype in the family was pure cerebellar ataxia. Homozygosity mapping revealed one large region of shared homozygosity at chromosome 19p13 between affected individuals. Within this region, whole-exome sequencing of the index case identified two novel homozygous missense variants in the PNPLA6 gene at c.3847G>A (p.V1283M) and c.3929A>T (p.D1310V) in exon 32. Both segregated perfectly with the disease in this large family, with only the two affected cousins being homozygous. We identified for the first time PNPLA6 mutations associated with pure cerebellar ataxia in a large autosomal-recessive Parsi kindred. Previous mutations in this gene have been associated with a more complex phenotype but the results here suggest an extension of the associated disease spectrum.