Genetic refinement of the hereditary neuralgic amyotrophy (HNA) locus at chromosome 17q25.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant, recurrent focal neuropathy. HNA is characterised by episodes of painful brachial plexus neuropathy with muscle weakness and atrophy, as well as sensory disturbances. Single episodes are commonly preceded by non-specific infections, immunisations or parturition. Mild dysmorphic features and short stature are present in some HNA families, but absolute co-segregation with HNA has not been described. To refine the previously described HNA locus on chromosome 17q25, we performed a genetic linkage study in five HNA families with different geographic origins. Significant linkage was obtained with chromosome 17q24-q25 short tandem repeat (STR) markers in three HNA families and suggestive linkage was found in the other two HNA families. Analysis of the informative recombinations in affected individuals allowed us to reduce the HNA linkage interval to a candidate region of 3.5 cM.

A novel 3'-splice site mutation in peripheral myelin protein 22 causing hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant, demyelinating peripheral neuropathy. Clinical hallmarks are recurrent painless focal neuropathies mostly preceded by minor trauma or compression at entrapment sites of peripheral nerves. In the majority of the patients, HNPP is caused by a 1.5 Mb deletion on chromosome 17p11.2-p12 containing the peripheral myelin protein 22 (PMP22) gene. Point mutations within this gene are reported in only a few families. We report a novel mutation in the PMP22 gene in a Spanish family with HNPP. The mutation is a 3' splice-site mutation, preceding coding exon 3 (c.179-1 G>C), causing a mild HNPP phenotype.

[Myositis with inclusion bodies: a little-known variety of idiopathic inflammatory myopathy]. / Miositis con cuerpos de inclusión: una variedad poco conocida de miopatía inflamatoria idiopática.

The authors report two male patients with inclusion body myositis (IBM) and review the features of this condition in the literature. This is an uncommon type of idiopathic myositis which involves males more often than females; it usually develops in elderly patients; its course is very slow; it is usually associated with distal weakness; neurophysiological studies show a mixed "myogenic" and "neurogenic" pattern; and it is usually unresponsive to corticosteroids. The diagnosis is basically made on the basis of the histological features, mainly consisting of vacuoles surrounded by a basophilic haze in histochemical stains of frozen tissue and, particularly, by the presence of characteristic microfilaments in ultrastructural studies.

[Central lesions in neurofibromatosis: clinical, MRI and histopathologic correlations. An attempted classification]. / Lésions centrales dans les neurofibromatoses: corrélations cliniques, d'IRM et histopahtologiques. Essai de classification.

The National Institute of Health Consensus Panel on Neurofibromatosis (NF) recently recognized 2 distinct forms of NF (NF-1 and NF-2) and stated that variant forms may exist. We selected 30 patients who fulfilled the criteria of NF-1 or whose condition was consistent with NF-2. All patients showed pathological magnetic resonance images (MRI), and in 19 cases confirmation was obtained from histopathology. We established correlations between the site and nature of the lesions on the one hand and the diagnostic criteria of NF on the other hand, there by hoping to contribute to a better knowledge and classification of neurofibromatosis. Nineteen patients had only intraparenchymatous lesions of the central nervous system (CNS) and fulfilled the criteria of NF-1; histopathological examination demonstrated pilocytic astrocytoma in 8 cases. Eleven patients showed only extra-axial lesions; 8 of them had criteria suggestive of NF-2, except for familial history. Pathological examination revealed either acoustic, pluriradicular, peripheral or mixed schwannomas (7/8) or pluriradicular ganglioneuromas (1/8). Two patients had unilateral extra-axial pluriradicular cervical lesions and fulfilled the diagnostic criteria of NF-1; pathological examination revealed neurofibroma in both cases. One female patient had both intra- and extra-axial lesions that fulfilled the criteria of NF-1 and NF-2, suggesting the existence of a mixed form (NF-3).

[A case of nemaline myopathy studied over a period of nine years (author's transl)]. / La myopathie némalinique (a propos d'une observation suivie pendant neuf années).

We report a case of a boy of 13 who was born with muscular hypotony which has tended to improve over the course of the years. We was examined for the first time when he was 4 years old and a diagnosis was made of "congenital myopathy". Examination showed curved feet, gothie palate, severe laxity of the ligaments, and spider fingers which evoked Marfan's syndrome. The present myopathy is concentrated in the shoulder girdle and the E.M.G. showed "myogenic" tracings. Biopsy of the deltoid showed the presence of large numbers of rods in all muscle fibers stained with Engel's modified trichromic stain, localized mainly under the sarcolemma. Histochemical staining showed no evidence of differences in the fibers, all of which had the same enzymatic activity. A diagnosis was made of nemaline myopathy. As we were able to follow clinical progress in this case for nine consecutive years we could confirm that not only was the disease non-progressive but that it was regressing in this patient.

[Aneurysmal vertebra cyst (observation on two cases with neurological findings) (author's transl)]. / Kyste anévrismal rachidien (à propos de 2 cas associés à des manifestations neurologiques).

The authors report 2 cases of aneurysmal cysts of the spinal cord with neurological manifestations. The first case was a young girl of 16 years of age with a lesion at the D6 level and spasmodic paraparesis. The second case was a boy aged 5 years with a lesions at the L3 level and lumbar pains. The characteristic "one-eyed vertebra" appearance was present in the radiological images in both cases, and was confirmed histologically on operation, which produced good results.

[Clinico-morphological correlations based on MRI in syringomyelia. Study of 22 cases]. / Corrélations clinico-morphologiques par I.R.M. dans la syringomyélie. Etude de 22 cas.

Twenty-two patients with syringomyelia were investigated clinically and by MR imaging using clearly defined clinical and radiologic protocols. Intramedullary cavities were identified by MR images in 20 cases and by CT scanning after intrathecal injection of Metrizamide in two cases. In all but one case, when the clinical picture was purely motor, concordance was established between clinical findings and morphologic type of intramedullary cavity. Syringomyelic syndromes should now be defined not only on the basis of clinical data but on clinicoradiologic features. The examination of choice is MR imaging, because of its reliability and safety and because it allows tridimensional analysis of cavities and associated malformations. Results of MR imaging exploration suggest a possible improved physiopathologic approach to the disease and more effective therapeutic procedures.

[3 cases of rare peripheral neuropathies associated with primary Gougerot-Sjögren syndrome]. / Trois cas de neuropathies périphériques rares associées au syndrome de Gougerot-Sjögren primitif.

Several forms of peripheral neuropathy occur in Sjögren's syndrome (dryness of eyes, mouth and other mucous membranes). Symmetrical sensorimotor polyneuropathy occurs most frequently followed by sensory neuropathy. Pure sensory neuronopathy, trigeminal sensory neuropathy and autonomic neuropathy are also common. We report three rare forms of peripheral neuropathy related to Sjögren's syndrome and analyze their clinical course and response to therapy. There were a case of mononeuropathy multiplex (MM), a case of recurrent cranial polyneuropathy (RCP) and a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). The patients were females, 70, 63 and 81 years old respectively. All of them fulfilled the criteria of Sjögren's syndrome, without clinical or serological abnormalities of systemic disease. Only one patient presented with positive antinuclear antibodies. In two patients the onset of neuropathy occurred before the sicca syndrome long. The sural biopsy of the patient with MM exhibited vasculitis of the small vessels and a mild sensory polyneuropathy was superimposed. The patient with RCP had 8 episodes of isolated third nerve palsy and 5 episodes of multiple cranial neuropathy. The patient with CIDP responded poorly to treatment while in the patients with MM and CRP the response to corticotherapy was good. In conclusion, Sjögren's syndrome must be considered in neuropathies of unknown cause not only when they are sensory, autonomic or trigeminal but also when they are recurrent suggesting an ischemic mechanism. Even a CIDP requires a search for Sjögren's syndrome before being considered idiopathic.

[Intermediate forms of infantile spinal amyotrophy. Apropos of 20 personal observations]. / Les formes "intermédiaires" de l'amyotrophie spinale infantile. A propos de vingt observations personnelles.

The authors report 20 cases of infantile spinal amyotrophy, including 8 sporadic and 12 familial. There were 10 boys and 10 girls, the age of onset of the disease being between 1 and 5 years, with an average of 32 months. The clinical course is such that these forms may be easily distinguished from the classical Werdnig-Hoffman syndrome, by virtue of their later onset and their slower progression. Intermediate forms also differ from the Kugelberg-Welander pseudo-myopathic form in developing earlier and having a less benign clinical course. These features favour the existence of a series of intermediate forms situated between the two classical types, the definition and limitations of the infantile spinal amyotrophies being relatively imprecise.

[Sensory-motor intermittent claudication syndrome of the cauda equina. Etiopathogenetic study of 25 cases]. / Syndrome de claudication intermittente sensitivo-motrice de la queue de cheval. Etude étiopathogénique de 25 cas.

The twenty-five patients with the intermittent claudication syndrome of th cauda equina included 19 men and 6 women aged from 23 to 70 years. The results of operation were very good in 16 cases, with improvement in 6 others and failure in 3 cases. There are various mechanisms which can cause the stenosis. The authors stress the importance of congenital vertebral abnormalities and the presence of apophyseal appendices which, at the present time, have not been considered responsible.

[Intracranial neurinoma of the spinal nerve (author's transl)]. / Neurinome intracranien du nerf spinal.

A patient aged 56 years has developed a syndrome affecting the last cranial nerves--IX, X, XI and XII--on the left side progressively over the last two years, and, more recently, deafness. Apart from a simple radiological examination all other radiological tests were negative. The diagnosis was made during the surgical operation which revealed a neurinoma of nerve XI (spinal) in its intracranial path. The diagnosis was confirmed histologically. After reviewing the published literature, the authors conclude that this is an exceptional case, which justifies publication and enables differential diagnosis to be made between this tumor and the Jugular Glomus tumor.

[Benign congenital myopathy with type I fiber predominance and rare "cores" in the asymptomatic mother. Association with malformations of the midline (author's transl)]. / Myopathie congénitale bénigne avec prépondérance des fibres de type I et rares "cores" chez la mère asymptomatique. Association avec des malformations de la ligne médiane.

The case of a 20 year-old female with a congenital myopathy and multiple midline malformations (cranio-facial dysplasia with cleft-palate, cervical and dorsal vertebral blocks and sacro-lumbar spina bifida) is reported. A muscle biopsy showed only a predominance of type I fibres (97,3 p. 100). A muscle biopsy from the asymptomatic mother showed a predominance of type I fibres (95 p. 100) and a small number of fibres (less than 5 p. 100) with central or peripheral cores. Other fibres showed subsarcolemnic mitochondrial aggregates and slight architectural alterations. These findings confirm the variable histological patterns in benign congenital myopathies and emphasize the usefulness of studying the asymptomatic parents of such patients in whom a predominance of type I fibres is the only change present in the muscle biopsy.

[Hemangioblastoma of the spinal cord. A case with a probably single lesion (author's transl)]. / Hémangioblastome intra-médullaire. Un cas sporadique avec une localisation apparemment unique.

A 43 year-old woman was admitted after 2 years of progressive disturbances of deep sensation mainly in her lower limbs. Examination led to the diagnosis of a tumor of the cervical spinal cord. The tumor--partially cystic--was attached to the posterior third of the spinal cord. At its level several varicosities of the pia were present accounting for the myelographic picture as well as for the albumino-cytologic dissociation in the CSF. Pathological examination showed a hemangioblastoma. After a review of the literature, this case of hemangioblastoma of the spinal cord appears to have special features because of its likely single location in the spinal cord in a patient without any familial history of phacomatosis or of von Hippel-Lindau's disease. No other lesion could be clinically suspected in the spinal cord. The post-operative evolution was satisfactory.

[A study of 14 cases of Bourneville's tuberous sclerosis, including two pathological reports and seven cases investigated by computer tomography (author's transl)]. / Etude longitudinale de 14 cas de sclérose tubéreuse de Bourneville (comportant l'étude anatomopathologique pour deux cas et la tomographie axiale computorisée pour sept).

The authors studied 9 girls and 5 boys, with ages ranging from 9 months to 26 years, suffering from Bournevilles tuberous sclerosis, for an average period of 7 years. The various types of epileptic attacks and their progression were studied as well as the degree of mental retardation. Only two of the children had a normal IQ. The accepted value of computer tomography examinations in this disease is confirmed. Pathological examinations were conducted in two cases, one complete (autopsy) and one partially only (histological examination of a paraventricular tumor removed by operation).

[Mitochondrial myopathy and leukoencephalopathy in twins of different sexes]. / Myopathie et leucoencéphalopathie mitochondriales chez des jumeaux de sexe différent.

Two 30-year old twins, one male, the other female, were followed up for 20 years for predominantly proximal muscular deficit without increase of muscle enzymes. The lactic acid level was elevated at rest and further increased during exercise. Muscle biopsy revealed mitochondrial abnormalities. Encephalopathy was also present. The female patient had been treated, at the age of 10 years, for myoclonic attacks which regressed when she was over 18 years. None of the two patients had dementia. CT and MRI showed very extensive and symmetrical lesions of the white matter which did not involve the basal ganglia. These two cases are interesting on three scores: (1) clinically, the woman exhibited symptoms of the MELAS syndrome (without cerebral vascular accidents) and symptoms of the MERRF syndrome, which suggests the existence of borderline cases; (2) genetically, our cases were in favour of a so-called "maternal" heredity (boys are affected in all cases): here both sexes were involved but the phenotype varied; (3) biochemically, we found no enzyme activity deficit likely to explain the clinical features. The significance of a selective increase of cytochrome c oxidase in both mother and daughter is unclear.

[Acute posterior cord lesions in multiple sclerosis. An MRI study of the clinical course in 20 cases]. / Lésions cordonales postérieures aiguës dans la sclérose en plaques.Etude clinico-évolutive et par IRM de 20 cas.

Twenty patients with multiple sclerosis (MS), 19 women and 1 man, with acute proprioceptive sensory disturbances related to the presence of plaques on the posterior columns (posterior column syndrome) at the cervical or thoracic levels of the spinal cord, were selected among 138 new patients with MS assisted in our neurological unit over the past five years. In 17 of these patients, the acute posterior cordonal syndrome was responsible for the first clinical manifestations of the disease. The other 3 patients had a history suggestive of MS. These 20 patients were followed with a minute analysis of neurological function with repeated clinical evaluation combined with repeated MRI study of the spinal cord. Brain MRI (strongly suggestive of MS in 15 patients), evoked potentials (EP) and cerebrospinal fluid electrophoresis analysis (with oligoclonal bands present in all patients were it was performed) were also obtained at least once in each patient. Spinal cord MRI demonstrated more lesions in the cervical region (90 p.100) than in the thoracic regions (10 p.100). Eighty percent of the cervical lesions were located high, between C1 and C4. The most characteristic clinical expression was the deafferentation of one upper limb, preferentially the "useless hand" (Oppenheim) or even a pseudoathetosic or dystonic limb. Propioceptive ataxia or spontaneous cervical or brachial pain were other forms of clinical expression. No major motor deficit or sphincter disorders were noted at any time in the clinical course in any of the patients. There was a good correlation between localization and morphology of the plaques detected by spinal cord MRI and clinical signs. Intrinsic medullary lesions were seen as high intensity signals on T2-weighted images which were enlarged more than the same lesion visualized on T1-weighted images after injection of paramagnetic contrast agents. This reflected the presence of edema extending beyond the main inflammatory lesion. There was also a good correlation between improvement of clinical symptoms and total or, mor frequently, partial reduction of the plaques, analyzed morphologically by successive spinal cord MRI series. The diagnosis of MS was clinically definitive in 60 p.100 of cases and laboratory-supported definitive in 40 p.100. During the follow-up period (average 36 months), 15 patients (75 p.100) presented one or more exacerbations, all of them presenting a favorable course: at last follow-up, 9 patients were asymptomatic, EDSS was 1 in 6 patients, 1.5 in 4 patients and 2 in 1 patient. This study confirms the contribution of serial spinal cord MR studies to understanding the natural history and pathophysiology of medullary forms of MS presenting as a cordonal posterior syndrome. It also shows a good relationship between the clinical manifestations and course of this form of MS and the localization and variable morphology of plaques. Finally, our results suggest the predictive benign course for this medullary form of MS that seems to be almost exclusively restricted to the female gender.

[Bilateral intra-axial involvement of the common oculomotor nerve (III): 2 cases]. / Atteinte bilatérale intra-axiale du nerf moteur oculaire commun (III): deux cas.

Bilateral palsy of the common ocular motornerve (III) was observed in two patients with an intra-axial lesion due ti hemorrhage in one and ischemia in the other. The lesions involved the cerebral peduncle in the periaqueductal region and the nuclear complex of the III in the first case. Bilateral infarct of the thalamus was seen in the second. Clinical manifestations were transitory except for the oculomotor impairment. In the first patient, oculomotricity was dissociated as intrinsic mortricity was spared. These exceptional cases demonstrate a syndrome with unique oculomotor expression resulting from intra-axial oculomotor lesions. Prognosis varies and is related to the ischemic or hemorrhagic nature of the causal lesion and its localization.

[Combined medullary hemangioblastoma and syringomyelia in a patient with von Hippel-Lindau disease: pathological study]. / Hémangioblastome médullaire associé a une syringomyélie dans un cas de maladie de von Hippel-Lindau: étude pathologique.

A patient presented with what was clinically diagnosed as a solitary medullary haemangioblastoma. One year later she was operated from a cerebellar haemangioblastoma. The neuro-radiologic findings showed all the characteristics of von Hippel-Lindau's disease, except the retinal haemangioblastoma. The patient died five years later as a result of deglutition problems with aspiration pneumonia. Post-mortem examination showed that the tumor level was in the posterior right side of the dorsal spinal cord. A syringomyelic cavity spread above the tumor up to the medulla - without communicating with the fourth ventricle and beneath the tumor down to the lowest part of the thoracic spinal cord. A large venous pia mater stasis and a thick glial wall of the cavity - mostly below the tumor - suggested a lack of reabsorption of liquids produced by the tumor.

[Machado-Joseph disease in a family of Spanish origin]. / Maladie de Machado-Joseph dans une famille d'origine espagnole.

The clinical observations in five patients, of a family of catalan origin (NE of Spain), affected with Machado-Joseph disease are reported. The pedigree showed the presence of 22 members affected (15 men, 7 women) over six generations. The symptoms and signs were variable among the patients and also variable in a same patient during the course of the disease. However, the main neurological alterations were ataxia, akinesia, distal amyotrophy, progressive external ophthalmoplegia, facial and lingual fasciculations and bulging eyes. The neuropathological examination performed in one patient disclosed degeneration of the posterior and spinocerebellar tracts in the spinal cord, marked nerve cell loss in Clarke's column and anterior horns and axonal degeneration of the peripheral nerves, in addition to nerve cell loss in the nuclei of the III, IV and VII cranial nerves and neuronal depletion in the substantia nigra. No other structures, including the striate complex and dentate nucleus, were significantly affected.

[Isolated angiitis of the central nervous system. Clinical and neuropathological study of 2 cases]. / Angéite isolée du système nerveux central. Etude clinique et neuropathologique de deux cas.

Isolated angiitis of the central nervous system (IAC) is an idiopatic, recurrent vasculitis confined to the CNS involving small blood vessels. We describe the clinical, angiographic, and neuropathological data in two patients with IAC and delineate the main clinical and neuropathological features in both cases as well as the importance of a complete autopsy for discovering subclinical vasculitic lesions outside the CNS. Patient 1 concerned a 40 year-old-man that evolved for the last three years, initially with focal seizures, headache, and neurological focal deficits, later on the left sided hemihyposthesia and preferentially left parieto-occipital dysfunctions. He presented an oligoclonal band in CSF with slight hyperproteinorraquia and 25 lymphocytes. A cerebral angiography was compatible with angiitis and a leptomeningeal/cerebral biopsy showed lymphocytic vasculitis in the leptomeningeal and intraparenchymatous cerebral small vessels. These results lead to start a treatment with Cyclophosphamide associated to high dose of steroids. The patient clearly improved and now is almost asymptomatic. Patient 2 concerned a 67 year-old-man that evolved for 4 years with encephalic ischemic lesions distributed and confined throughout the brain stem and cerebellum, temporary remissions occurred and the patient required high-dose steroids and Cyclophosphamide to improve. Conventional and MRI angiographies only suggested the diagnosis that was confirmed at autopsy. The patient died after a massive pulmonary thromboembolism and a complete necropsic study showed abundant lymphocytic infiltrates, without granulomatous lesions, in the intraparenchymatous and leptomeningeal cerebral small vessels specially at the brain stem and cerebellar level where many demyelinated greyish areas and few infarctions were to be seen. The inflammatory cells were, in both cases, predominantly CD4+ T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)