[Facial diplegia and acute inflammatory demyelinating neuropathy secondary to varicella]. / Diplégie faciale au cours d'une neuropathie démyélinisante inflammatoire aiguë secondaire à une varicelle.

INTRODUCTION: Primo-infection by varicella-zoster virus (VZV) may be associated with several neurologic complications. Bilateral facial palsy is a rather uncommon manifestation. CASE REPORT: We report the case of a 38-year-old woman who developed bilateral facial diplegia and paresthesia affecting all four limbs with subacute onset several days after varicella virus primoinfection. Ancillary tests showed hyperproteinorachia and signs of demyelinating polyneuropathy in nerve conduction tests. The diagnosis of Guillain-Barré syndrome was retained and a treatment with intravenous immunoglobulines was started, leading to progressive improvement. CONCLUSION: Immunotherapy is a possible therapeutic approach in the context of neurologic postinfectious complications after VZV infection where an underlying mechanism is probable.

[Fragile X premutation presenting as postural tremor and ataxia (FXTAS syndrome)]. / Tremblement postural et ataxie révélant une prémutation X fragile ou syndrome FXTAS.

We report a case of FXTAS in a 58-year-old man who presented with postural tremor, mild ataxia and dysexecutive cognitive signs. The syndrome had a slow progressive course. Brain imaging by MRI showed characteristic abnormalities with mild cerebellar atrophy, symmetric high signals in the middle cerebellar peduncles and in the subcortical white matter of cerebral hemispheres. The diagnosis was confirmed by molecular genetics showing by southern blot a 100-120 expansion repeat of the CGG trinucleotide. FXTAS is a recently described syndrome, still unknown by most neurologists and probably rather frequent in men older than 60. We emphasize the value of clinical evaluation and brain imaging by MRI in some patients presenting with non specific motor or cognitive symptoms. A diagnosis of FXTAS may have implications for genetic counselling of female relatives.

[Apolipoprotein E and bleomycin hydrolase. Polymorphisms: association with neurodegenerative diseases]. / Maladies neurodégénératives et polymorphisme des gènes de l'apolipoprotéine E et de la bléomycine hydrolase.

Several studies indicate a possible association between different genes and chronic neurodegenerative diseases including Alzheimer's disease (DTA). To further investigate, we have analyzed association between the apolipoprotein E (apo E) and bleomycin hydrolase (BH) polymorphisms and three groups of elderly patients: control subjects (T) (n = 68), late-onset sporadic DTA patients (DTAst) (n = 65) and other non vascular neurodegerative diseases (MNDA) (n = 52). Apo E-epsilon4 and BH-G alleles frequencies (%) are: 8.2 (T), 31.5 (DTAst), 16.4 (MNDA) and 41.4 (T), 35.6 (DTAst). No association has been observed between carrying the G allele and DTA in epsilon4 negative subjects but, our data have confirmed the earlier reports: carrying the epsilon4 allele is a dose-dependent risk factor for the DTAst (OR: 6.0, IC 95 %: 2.6-13.7) and decrease the age of symptom onset (p < 0.005). They have also suggested that apo E genotyping may be of interest to perform differential diagnosis of neurodegenerative diseases in elderly subjects.

[Atypical CADASIL phenotypes and pathological findings in two new French families]. / CADASIL: aspects phénotypiques inhabituels et observations anatomo-pathologiques dans deux nouvelles familles françaises.

Atypical phenotypes of CADASIL and corresponding anatomical data in two cases are described in 6 members of 2 new French families. In the first family, 4 cases in the same kindred were probably affected, two of them with a predominant psychiatric presentation, two others with dementia and a pseudo-bulbar syndrome of progressive evolution. No history of migraine or ischemic event were documented in any. In the propositus, the diagnosis was documented by skin biopsy, Notch 3 gene mutation and autopsy after the patient had died when 67 years old, 8 years after onset. Brain examination showed a widespread leukoencephalopathy with subcortical infarcts. Characteristic granular lesions of the small arteries of the brain and other organs were observed. In the second family, two cases are reported. One patient died when 63 years old after a subacute evolution mimicking intracranial hypertension. The anatomical diagnosis was retrospectively proven typical of CADASIL with Notch 3 immunostaining of arterial smooth muscle cells. The other case had a progressive evolution over 20 years of limb paresthesia with a mild spasticity diagnosed as a progressive form of multiple sclerosis. It was followed by a pseudo-bulbar syndrome and a mild subcortical dementia without acute ischemic attack. The diagnosis was confirmed by skin biopsy and mutation of the Notch 3 gene. This report illustrates

[Tuberculous meningitis in an immunocompetent adult: contribution of cerebral imaging techniques to the diagnosis and follow-up]. / Méningite tuberculeuse de l'adulte sans immunodépression acquise: contribution de l'imagerie cérébrale au diagnostic et au suivi évolutif.

We have studied 5 men, mean age 47 years, affected by tuberculous meningitis (TM) without documented immunodepression. The diagnosis of TM was supported by clinical and biological investigations and confirmed by the cultures of CSF. All the patients received a four-drug combination therapy and steroids. No drug resistance of the bacilli was observed. Cerebral imaging by CT and MRI was rarely diagnostic but most useful during the follow-up. All the patients developed complications including tuberculomas (5), hydrocephalus (4), ischemic lesions (2), arachnoiditis (1) and abscess of spinal cord (1). Four patients recovered and one died. The mean duration of the follow-up was 16 months. MRI was more sensitive than CT scan to identify inflammatory lesions such as granulomas, angeitis or arachnoiditis and to follow their outcome. Tuberculomas and hydrocephalus were easily diagnosed by CT scan with contrast enhancement. Recommendations of sequential imaging are suggested to identify unexpected or asymptomatic complications of TM during therapy and evaluate the outcome.

CADASIL: a review with proposed diagnostic criteria.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered as a new disease predominantly affecting the small vessels of the brain with an autosomal dominant transmission linked to chromosome 19. This review includes an historical perspective showing how the disease was identified from the spectrum of vascular leukoencephalopathies. More than two hundred patients have now been described, belonging to at least 30 unrelated pedigrees in Europe, America and Asia. The clinical features include four major neurological presentations associated in variable degrees during the course of the disease: migraine with or without aura, strokes or stroke-like episodes, major psychiatric symptoms and dementia. The patients are free of the classical vascular risk factors. The disease has a progressive or stepwise course with age at onset in the forties and a mean duration of 13.6 +/- 10.7 years. Death occurs in the fifties in a characteristic condition associating a pseudo-bulbar syndrome and subcortical dementia. Cerebral magnetic resonance imaging (MRI) is highly contributive to the diagnosis, showing a diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter. Pathological data show macroscopic lesions similar to Binswanger's disease but different lesions of the small vessels including thickening of the media, characteristic PAS+ granular material and narrowing of the lumen. Skin biopsy may be a valuable diagnostic tool, showing ultrastructural alterations of skin vessels similar to those of brain vessels. The disease is highly homogeneous on a genetic basis and the identification of the gene Notch 3 on chromosome 19 has opened new avenues for research and genetic counselling. The pathogenesis of the disease has still to be elucidated. A definite diagnosis relies on genetical or pathological data. Diagnostic criteria are proposed to recognize the disease on clinical and imaging parameters. So far, no treatment has been reported to be successful for CADASIL. Copyright Lippincott-Raven Publishers

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, genetic homogeneity, and mapping of the locus within a 2-cM interval.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently identified autosomal dominant cerebral arteriopathy characterized by the recurrence of subcortical infarcts leading to dementia. A genetic linkage analysis conducted in two large families recently allowed us to map the affected gene on chromosome 19 in a 12-cM interval bracketed by D19S221 and D19S215. In the present study, these first 2 families and 13 additional ones, including a total of 199 potentially informative meiosis, have been genotyped with eight polymorphic markers located between D19S221 and D19S215. All families were linked to chromosome 19. The highest combined lod score (Zmax = 37.24 at theta = .01) was obtained with marker D19S841, a new CAn microsatellite marker that we isolated from chromosome 19 cosmids. The recombinant events observed within these families were used to refine the genetic mapping of CADASIL within a 2-cM interval that is now bracketed by D19S226 and D19S199 on 19p13.1. These data strongly suggest the genetic homogeneity of this recently identified condition and establish the value of its clinical and neuroimaging diagnostic criteria. Besides their importance for the ongoing positional cloning of the CADASIL gene, these data help to refine the genetic mapping of CADASIL relative to familial hemiplegic migraine and hereditary paroxysmal cerebellar ataxia, conditions that we both mapped within the same chromosome 19 region.

Myelitis due to varicella-zoster virus in two patients with AIDS: successful treatment with acyclovir.

Only a few cases of varicella-zoster virus (VZV) myelitis have been described, and nearly all have been diagnosed post-mortem. There have been no reports in the literature of successful treatment of VZV myelitis with antiviral medications. We report on two patients with AIDS who had acute severe myelitis accompanied by herpes zoster. The presence of VZV DNA in cerebrospinal fluid (CSF) was documented by the polymerase chain reaction (PCR) technique. Early treatment with acyclovir was followed by a slow but complete recovery after a phase of initial aggravation. After a follow-up of > 1 year, the two patients remained asymptomatic. We conclude that (1) VZV should be considered a curable cause of myelitis in patients with AIDS, (2) PCR assay of CSF will assist in early diagnosis, and (3) early treatment with acyclovir should aid in recovery.

[Cadasil--a new model for subcortical dementia]. / Cadasil--un nouveau modèle de démence sous-corticale.

We report 3 cases of Cadasil with dementia. In the 3 cases, the dementia had a subcortical and frontal presentation. It associated behavioural symptoms, amnesia, executive functions disturbances, bradyphrenia, slowing of information processing and frontal symptoms, without aphasia, apraxia or agnosia. One patient showed overt dementia before any focal neurological sign. Imaging of the brain was consistent with subcortical infarcts and leukoencephalopathy, without involvement of the cerebral cortex. We suggest that dementia and psychoaffective disturbances are major diagnostic criteria for Cadasil. This pathology is probably a good model for the neuropsychological study and the physiopathological analysis of the concept of subcortical dementia.

A prospective study of depression in French patients with Parkinson's disease. The Depar study.

To investigate the prevalence and symptomatology of depression in Parkinson's disease (PD), we have studied 506 unselected patients attending the neurology services in French general hospitals during a 5 month period defined for prospective inclusion. 246 patients (48.6%) were suspected of depression according to different methods of evaluation and 168 (33.2%) were defined as definite or probable depression. According to the Montgomery and Asberg scale, 46 cases (9%) had a severity score suggestive of major depression. As a function of the cut-off score defined for severity, these patients represented from 23.2 to 43.7% of the depressive population with PD. There was no significant difference between depressed and non depressed PD patients as a function of the patient's current age or age at onset of PD. A significantly higher rate of depression was found among women with PD. A past history of depression was a risk factor for mood disorder after onset of PD. The severely depressed patients had a significantly longer duration of PD and a higher score of cognitive impairment than mildly or moderately depressed and non depressed patients with PD. Depressed patients had a significantly more advanced stage of disability than non-depressed patients with PD.

Transcortical alexia with agraphia following a right temporo-occipital hematoma in a right-handed patient.

We describe the case of a 51-year-old right-handed man who was affected by a transcortical alexia with agraphia and aphasia. Transcortical alexia produces errors in both reading and writing while copying is preserved. The patient had a severe alexia and was unable to read letters, words or sentences. Language examination showed mild aphasia with reduced fluency, intermittent paraphasia but a good comprehension and a normal repetition. Spontaneously and from dictation, writing was impaired by an agraphic jargon, but copying was excellent even though the patient was unable to read his own written production. There was no visual agnosia nor hemianopia. CT scan and MRI of the brain showed that there was a single right temporo-occipital hemorrhage but no lesion in the left hemisphere. Following surgical evacuation of the hematoma, the patient improved. One month after onset, his language was quite intact and reading was possible. We hypothesize that this particular syndrome was the result of a double disconnection: alexia would result from a disconnection of the right angular gyrus and the occipital associative areas by a subangular lesion; agraphia would result from a disconnection of the right angular gyrus and the semantic store, probably located in the right hemisphere.

[Cerebral hemorrhage disclosing metastatic choriocarcinoma]. / Hémorragie cérébrale révélatrice d'un chorio-carcinome métastasé.

We report the case of a 28-year-old woman who presented with multiple episodes of cerebral bleeding secondary to a choriocarcinoma with brain, lung and abdominal metastases, which had been partially treated 1 year before. The diagnosis was confirmed by a-high serum beta HCG level. This case emphasizes the importance of suspecting an underlying choriocarcinoma and obtaining a serum beta HCG level in young women presenting with a cerebral haemorrhage.

[Chorea disclosing polycythemia and renal adenocarcinoma]. / Chorée révélatrice d'une polyglobulie et d'un adénocarcinome rénal.

A 79-year-old woman had chorea complicating polycythaemia. The polycythaemia and the chorea disappeared after surgical removal of a renal carcinoma. The literature on polycythaemic chorea is reviewed and its pathophysiology discussed.

[Familial subcortical dementia with arteriopathic leukoencephalopathy. A clinico-pathological case]. / Démence sous-corticale familiale avec leucoencéphalopathie artériopathique. Observation clinico-pathologique.

A 54-year-old man died after a subcortical dementia that had developed over 7 years with focal neurological signs and a stepwise course. Clinical and radiological features were similar to those of Binswanger's disease but there was no vascular risk factor, especially no hypertension. Three similar cases had occurred in the family affecting the patient's mother, her brother and sister, suggesting an autosomal dominant hereditary disease. Postmortem examination disclosed an arteriopathic leukoencephalopathy. The white matter was mainly affected in the periventricular areas of the frontal and parietal lobes with myelin loss and pallor, sparing the U fibers. The vascular changes involved the small vessels and were not arteriosclerotic. There was severe thickening of the internal lamina and degradation products of the elastic fibers. There was no amyloid. This vascular leukoencephalopathy was different from Binswanger's disease and amyloid angiopathy. We think that the vascular lesions could correspond to a genetically transmitted specific degenerative pathology of the small arteries of the brain.

[Neuropathologic validation of clinical diagnosis of senile dementia of the Alzheimer type]. / Validation neuropathologique du diagnostic clinique de démence sénile de type Alzheimer.

The purpose of this work was to establish a neuropathological confirmation of the clinical diagnosis of senile dementia of the Alzheimer type (SDAT) in a group of patients prospectively studied in a geriatric hospital since 1984 (Charles Richet Study). The sample consisted of 45 cases, 35 of which had received a clinical diagnosis of SDAT and 10 others a diagnosis of either vascular or mixed dementia. The mean age at death was 85 +/- 6.9 years (range 64-97). The neuropathological diagnosis was established independently of the clinical findings. Senile lesions typical of SDAT were found in 32/35 cases, giving a 91.4% rate of clinico-pathologic agreement. However, vascular lesions were present in 10 cases (28.5%) and the final pathologic diagnosis was mixed dementia, lowering the score of agreement for SDAT to 63%. Considering that the pathological criteria for the diagnosis of SDAT are not uniform, we independently applied 3 inclusion (senile lesions) and 3 exclusion (vascular lesions) criteria for the diagnosis of SDAT to each of the 45 cases. This permitted a comparison of nine combinations of neuropathological criteria with the clinical diagnosis. The sensitivity values ranged from 37 to 80% and the specificity values ranged from 55 to 100%. The highest agreement rate with the clinical diagnosis was achieved when were associated the criterion which specified that plaques and tangles must be present in the hippocampus regardless of neocortical findings and the criterion which excluded cases with vascular lesions of any site if their volume was 50 ml or more.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mitochondrial encephalopathy affecting only the central nervous system]. / Encéphalopathie mitochondriale avec atteinte exclusive du système nerveux central.

A 32 year-old diabetic woman presented with an acute coma followed by epileptic seizures, aphasia and constructive apraxia. No ischemic lesion was demonstrated by CT scan and carotid angiograms. The other investigations showed sensorineural hearing loss, retinal degeneration, calcifications of the basal ganglia and lactic acidosis. The follow-up was marked by pseudo-dementia with personality disorders, memory deficits, behavioural changes, migrainous and epileptic features. Although there was no sign of muscular deficiency, a muscular biopsy showed characteristic ragged-red fibers and mitochondrial abnormalities at electron microscopy. The muscular biopsy enables us to classify this case as a mitochondrial encephalopathy similar to the MELAS syndrome. The stroke-like episodes are probably caused by a specific angiopathy involving the mitochondria of brain vessels.

Senile dementia of the Alzheimer type: is there a correlation between entorhinal cortex and dentate gyrus lesions?

Senile plaques (SP) are one of the neuropathological hallmarks of senile dementia of the Alzheimer type (SDAT). In 14 patients affected with SDAT (over 74 years of age), thioflavine S, Tau and acetylcholinesterase (AChE) stainings demonstrated an increased density of SP in the outer two thirds of the dentate gyrus molecular layer. However, a wide range of SP density was observed among the cases. The molecular layer of the dentate gyrus is one of the termination site of the perforant pathway that originates in layers II and III of the entorhinal cortex. We have found that the number of AChE-, thioflavine S- and Tau-positive SP that accumulate in the dentate gyrus is positively correlated with the density of thioflavine S-stained neurofibrillary tangles in layers II and III of the entorhinal cortex. In contrast, a similar correlation is not found when using Tau immunolabeling of the entorhinal tangles. These observations show an association between the accumulation of AChE-positive SP in the dentate molecular layer and the lesions of the perforant pathway. Furthermore, they suggest that the density of SP in the dentate gyrus correlates with the late stages of neurofibrillary tangles formation (thioflavine S positive), but not with the early stages (Tau positive).