Phenotypic variability in familial prion diseases due to the D178N mutation.

BACKGROUND: Between January 1993 and December 2003, 19 patients with familial prion diseases due to the D178N mutation were referred to the regional epidemiological registry for spongiform encephalopathies in the Basque Country in Spain, a small community of some 2,100,000 inhabitants. METHODS: Ten further patients belonging to the same pedigrees were retrospectively ascertained through neurological or neuropathological records. In four of the patients, the diagnosis was confirmed by analysing DNA obtained from paraffin blocks. In this article, we report on the clinical, genetic, and pathological features of the 23 patients carrying the D178N mutation confirmed by genetic molecular analysis. Haplotyping studies suggest a founder effect among Basque born families, explaining in part this unusually high incidence of the D178N mutation in a small community. Only two patients (8%) lack familial antecedents. RESULTS: We have observed a phenotypic variability even among homozygous 129MM patients. Our findings challenge the currently accepted belief that MM homozygosity in codon 129 is always related to a fatal familial insomnia (FFI) phenotype. Indeed, seven out of 17 patients with a 129MM genotype in this series presented with a Creutzfeldt-Jakob disease (CJD) clinicopathological picture. CONCLUSIONS: The considerable clinical and pathological overlapping observed among homozygous 129MM patients favours the view that FFI and CJD178 are the extremes of a spectrum rather than two discrete and separate entities. Other genetic or environmental factors apart from the polymorphism in codon 129 may play a role in determining the phenotypic expression of the D178N mutation in the PRNP gene.

[Dementia with frontal lobe atrophy: clinical study from 18 patients with cognitive impairment and frontal lobe involvement detected by structural and functional neuroimaging]. / Demencia con atrofia frontal: estudio clínico de 18 pacientes con deterioro intelectual y degeneración de los lóbulos frontales según la neuroimagen.

OBJECTIVE: To characterize clinically patients with cognitive impairment and frontal lobe degeneration at neuroimaging. PATIENTS AND METHODS: Patients diagnosed of dementia or mild neurocognitive impairment by DSM IV criteria and neuropsychological tests with frontal lobe atrophy and hipoperfusion detected by computed tomography and single photon emission computed tomography. RESULTS: 18 patients, 5:1 on behalf of women; mean age at onset, 74 years; hereditary for dementia, 38%; mean duration of illness at first testing, 2 years; the most common initial symptoms, memory loss. At initial examination, psychotic or behavioral impairment was found in 61% and parkinsonism in 38%, the commonest cognitive troubles at this moment was the executive function, language and anterograde memory dysfunctions at the same rate. Frontal lobe atrophy and hypoperfusion was found in 100%, temporal in 88% and parietal in 38%. Electroencephalogram was pathological in 33%. The course of the disease was progressive but with fluctuation in 27%. Frontotemporal dementia clinical criteria in 13 patients, 4 of them clinical criteria of dementia with Lewy bodies too, and clinical criteria of Alzheimer s disease in 5.

[Symptomatic paroxysmal dystonia (non-kinesigenic forms): two new cases]. / Distonía paroxística sintomática (variedad acinesigénica): dos nuevos casos.

We report two new cases of symptomatic paroxysmal non-kinesigenic dystonia. The first is a 68-year-old woman with paroxysmal spontaneous dystonic spasms in her right arm lasting 1 minute. They occurred 1-2/day, a few months after a cerebral infarction (left internal capsule and left lenticular nucleus) which occurred 6 years ago. The second is a 30-year-old woman with a 7-year-history of spontaneous dystonic postures (flexion spasms) in her left arm lasting 15 minutes and occurring monthly. In this case an Arnold-Chiari malformation with cervical syringomyelia was discovered.

[Risk of the development of dementia after interruption of zidovudine treatment]. / Riesgo de desarrollo de demencia tras la interrupción de un tratamiento con zidovudina.

BACKGROUND: Epidemiologic data suggest that zidovudine (ZDV) could prevent the AIDS dementia complex (ADC), but this hypothesis has been specifically studied. PATIENTS AND METHODS: We have reviewed the medical records of all patients with human immunodeficiency virus (HIV) infection admitted to our section between January 1990 and December 1993 who were diagnosed with ADC, and we have compared them to those of a control group with regard to the interruption of ZDV at least 3 months before. Controls were selected from the remaining HIV-related admissions, matched by calendar year, CD4-cell count and previous HIV-disease stage. RESULTS: Thirty-nine cases and 39 controls were available for analysis; twenty-nine (74%) and 25 (64%) were male. The median age was similar for both groups: 30. Thirty-one patients (79%) in each group had a previous diagnosis of AIDS, six (15%) in each group had an AIDS-related complex and in two (5%) the ADC was the first complication of their HIV disease. The median CD4-cell counts were 79.6 and 79.4 x 10(6)/l. Twenty-three patients in each group had taken ZDV. Six of these from the ADC had withdrawn treatment, as compared to 2 from the control group (odds ratio [OR] 3.36; 95% confidence interval [CI]: 0.54-35.76). On the other hand, 16 patients with ADC were still on ZDV at the time of diagnosis, as compared to 21 controls (OR: 0.66; 95% CI: 0.22-1.60). CONCLUSION: In this case-control study, the interruption of treatment with ZDV was not found to be a risk factor for the development of ADC.

[Idiopathic cervical plexopathy]. / Plexopatía cervical idiopática.

We describe a 26 year-old woman with cervical plexopathy with damage of left superficial or cutaneous branches, and left cervical sensory dorsal rami. Picture began acutely and vanished few days later. We ruled out known etiologies like traumatisms, tumours and surgical and anaesthetic complicated procedures, therefore the patient suffered an idiopathic cervical plexopathy. We hypothesize two possibilities for this clinical picture: an autoimmune reaction or a muscular entrapment.

Operculum syndrome in childhood: a rare cause of persistent speech disturbance.

An infant is described who developed operculum syndrome during an acute encephalitic illness. Presenting symptoms were cortical pseudobulbar palsy and focal seizures of facial origin. Persistent mutism--with normal language comprehension and orofacial motor disturbance--were the main neurological sequelae. Similarities between this case and other permanent or transient causes of cortical pseudobulbar palsy are discussed, as well as the possible relationship with certain types of childhood language disorders.

[Cryptococcal meningitis and AIDS. Clinical description of 10 patients]. / Meningitis criptocócica y SIDA. Descripción clínica de 10 pacientes.

We have studied 10 patients with cryptococcal meningitis and AIDS. Nine of them were intravenous drug users and four have been previously diagnosed of AIDS. In 60% of them cryptococcal meningitis was the first opportunistic infection, and as group represented only 6.3% of our 158 patients with AIDS on the same period. The most common symptoms were: malaise (100%), headache (80%), fever (60%), meningeal signs (50%). Two of them had focal neurological disease. CSF culture and serum cryptococcal antigen test were positive in 90%, the Indian ink in 77% and blood cultures in 30% of the cases, while indian ink preparation did it in 77%. MRI showed bilateral small lesions, deeply located, in 3 cases; it was also useful to prove optical tract lesions in a patient with blindness as a result of cryptococcal meningitis. We had treatment successes in 80% of the cases, all patients being treated with amphotericin B, alone in 4 and amphotericin B plus fluorocytosine in 6. Two patients died within the first 2 weeks. Maintenance therapy with fluconazole was effective and well tolerated, with 3 patients dying from causes other than cryptococcal meningitis. We recorded a survival rate over 12 months in 33% of patients.

[Use of magnetic resonance in the diagnosis of neuro-cryptococcosis in the acquired immunodeficiency syndrome: study of 4 patients]. / Aportación de la resonancia magnética al diagnóstico de la neurocriptococosis en el síndrome de inmunodeficiencia adquirida: estudio de 4 enfermos.

Neuro-cryptococcosis is a common opportunistic infection in AIDS or HIV infected patients. From a series of 10 neuro-cryptococcosis the four of them studied by magnetic resonance (MR) are reported. In AIDS patients a high suspicion of opportunistic infection of the CNS is needed as exemplified by two of the four patients who only presented cephalalgia. The other two patients suffered additional symptoms and signs of meningeal and CNS involvement, such as nuchal rigidity, cranial nerve palsies, papilloedema, gait ataxia and dismetria. Diagnosis was achieved (confirmed) by a positive culture, serology or indian ink test in CSF. CT scan did not contribute to the diagnosis and management of the patients. In contrast MR, showed in three of them a peculiar pattern of small, confluent, high-signal lesions, roughly symmetrically placed in the basal ganglia and the internal capsule. They probably correspond to the dilated Virchow-Robin spaces through which torulae migrate from the subarachnoid space.

[Idiopathic cerebral gas embolism]. / Embolia gaseosa cerebral idiopática.

Air embolism to the brain is an accident that may occur in situations that favour the entrance of air into the bloodstream. The clinical diagnosis is sometimes difficult and only the computerized axial tomography may be of invaluable help. We present a rare case of air embolism occurring during sleep in which no apparent causes could be established. This woman had clinical findings of extensive infarction at the right cerebral hemisphere. The axial tomography performed during the first five days showed the presence of air bubbles persisting for three days and areas of infarction and edema during the 3rd-5th day. Magnetic resonance evidenced new areas of infarction in both hemispheres by the 12th day. Application of antiedema therapy was followed by a partial clinical recovery.