G. Sanges

Mapping of a Gene for Parkinson's Disease to Chromosome 4q21-q23

Parkinsons disease (PD) is the second most common neurodegenerative disorder after Alzheimers disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

Cognitive impairment in systemic lupus erythematosus: a follow-up study

Abstract We evaluated outcome and the clinical value of cognitive impairment in systemic lupus erythematosus (SLE). Fifty-one consecutive SLE subjects with or without overt nervous system involvement received two comprehensive neuropsychiatric and neuropsychological assessments, including the Mental Deterioration Battery, the Mini Mental State Examination (MMSE), and tests from the Wechsler Adult Intelligence Scale. The two neuropsychological assessments were made when subjects were in stable neurological condition. Twenty-seven patients were found to have neuropsychiatric symptoms (NP-SLE) at the first assessment, and three others developed them during the follow-up. Fifteen patients (10 NP-SLE) had cognitive impairment at the first assessment. At retest the cognitive deficit persisted in all patients but one (non-NP-SLE) and had developed in four others. In the cognitively impaired subjects scores on MMSE approached the cutoff for an overt dementing condition. No progressively decreasing scores were found on any of the tests. No relationships were shown between neuropsychological diagnosis and neuropsychiatric disorder, neuroradiological findings, disease activity, or steroid and nonsteroid immunosuppressive therapy. Cognitive impairment thus seems to be a stable symptom of CNS involvement in SLE. It corresponds to the subjective complaint of intellectual difficulties and marginal performance on the MMSE. Intellectual deterioration may occur in patients without other symptoms of NP-SLE. Standardized neuropsychological testing methods should be used routinely to assess SLE patients.

Lack of sodium channel mutation in an Italian family with paramyotonia congenita

OBJECTIVE To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). BACKGROUND PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A, the gene encoding the alpha-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. METHODS We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. RESULTS Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR-single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A. CONCLUSION The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Craniofacial pain followed by scalp necrosis and stroke. An unusual presentation of the primary antiphospholipid syndrome.

Sirs: Antiphospholipid syndrome (APS) is a condition characterised by recurrent arterial and venous thromboses and spontaneous abortions, related to the presence of circulating anticardiolipin antibodies (aCLs) [1, 3]. Migraine, retinal thrombosis, recurrent transient ischaemic attacks TIAs) and cerebral stroke [2–4] are common clinical manifestations. Necrotising skin lesions of the limbs and digits [1, 5] have often been reported. We describe a case of primary APS with atypical onset: craniofacial pain and diffuse scalp necrosis, followed by an ischaemic stroke in the right parietal subcortical white matter. A previously healthy 70-year-old man with no risk factors for cerebrovascular disease presented with subacute paraesthesias and burning pain involving his scalp and maxillary region bilaterally. Movement exacerbated symptoms. These worsened at night. Neurological and ophthalmological studies and the examination of the scalp were unremarkable. There was no fever or symptom of systemic disease. Blood routine was unremarkable, except for a slight increase in erythrocyte sedimentation rate (ESR; 22 mm/h). Tomography of the temporomandibular joints and skull and brain computed tomography (CT) were normal. The patient was diagnosed as having a craniofacial pain syndrome of undetermined origin and discharged with symptomatic therapy: imipramine 75 mg/ day and alprazolam 1.5 mg/day. One week later the patient developed a wide scalp necrosis, followed a few days later by stroke. Clinical examination at re-admission revealed diffuse scalp necrosis, left hemiparesis and hemineglect. Cranial magnetic resonance imaging (MRI) showed a wide area (hypointense in T1-weighted and hyperintense in T2-weighted images) on the right parietal convexity. Duplex continuous wave (CW) scanning of supraaortic arteries and echocardiography showed no abnormality. Blood count revealed leucocytosis (13.9 × 109/l granulocytes exceeding 80% of the total count). Platelet count was 140 × 109/l. ESR was 59 mm/h. Serum immunoglobulins, C3 and C4 fractions were normal. Rheumatoid arthritis (RA) test, Waaler-Rose reaction, antinuclear antibodies (detected by indirect immunofluorescence on Hep-2 cell lines) were below their baseline. Cryoglobulins were undetectable. Systemic infections were excluded by culture and serological studies. Multiple scalp biopsy specimens showed hair follicle necrosis with perifollicular mononuclear inflammation. Superficial temporal artery biopsy (15 mm) revealed intimal hyperplasia and a partially organised intraluminal thrombus. Immunohistology, using specific antisera (LC-Dako) and antibodies (KP1-Dako), revealed a few scattered leucocytes and macrophages in the adventitia. Lymphocytes and giant cells were absent. Serum aCL titres, measured by a standardised solid-phase enzyme-linked immunoassay, were highly positive: IgM (MPL) were 86 U/ml, and IgG (GPL) 96 U/ml. Therefore, the patient was suffering from a primary APS. A low-dose aspirin regimen (75 mg/day) was immediately initiated. Imipenem-cylastatin (1.5/day) was given for 15 days in addition to topical therapy for the skin lesions. Re-epithelialisation of necrotic areas occurred in a few weeks (Fig.1). The LETTER TO THE EDITORS J Neurol (1999) 246 :134–135