Charcot-Marie-Tooth disease type 4C4 caused by a novel Pro153Leu substitution in the GDAP1 gene.

Charcot-Marie-Tooth type 4C4 disease (CMT4C4) is an early onset, autosomal recessive neuropathy with hoarseness caused by mutations in the GDAP1 gene which maps to the 8q13 region. To date, only 24 mutations in the GDAP1 gene have been reported. Neuropathological findings of sural nerve biopsies have been published for a limited number of CMT4C4 patients. Herein, a novel Pro153Leu mutation in the GDAP1 gene identified in a consanguineous Polish family is described and longitudinal clinical and electrophysiological studies as well as morphological findings are presented.

Early onset Charcot-Marie-Tooth disease caused by a homozygous Leu239Phe mutation in the GDAP1 gene.

Mutations in the ganglioside -induced differentiation-associated protein 1 (GDAP1) gene are common a cause of the Charcot-Marie-Tooth (CMT4A) disease with autosomal recessive mode of inheritance. To date more than twenty mutations in the GDAP1 gene have been reported in patients suffering from the demyelinating, axonal or mixed form of Charcot-Marie-Tooth disease. Only in a few CMT4A affected patients sural nerve biopsy findings have been provided. We report a homozygous Leu239Phe mutation in the GDAP1 gene in a 39-year-old female with a severe form of mixed axonal and demyelinating Charcot-Marie-Tooth disease.

Progressive myopathy in hyperkalemic periodic paralysis.

A progressive degenerative myopathy has been well described in hypokalemic periodic paralysis but is not as widely recognized in hyperkalemic periodic paralysis. We studied four families with the latter disease in which some members developed a progressive myopathy. Episodes of paralysis were prolonged, lasting for months in some cases, and in one case paralysis was sufficiently severe to require ventilatory support. The progressive myopathy tended to develop at a time when attacks of paralysis were decreasing in frequency. Muscle biopsy specimens showed variability in fiber size, internal nuclei, and fibers with vacuoles. Electron microscopy showed myofibrillary degeneration and tubular aggregates. An abnormal biopsy specimen was more common in older patients. Our experience suggests that a progressive myopathy is as common in hyperkalemic periodic paralysis as it is in the hypokalemic disorder.

A novel mutation, Thr65Ala, in the MPZ gene in a patient with Charcot-Marie-Tooth type 1B disease with focally folded myelin.

Charcot-Marie-Tooth type 1B disease is a demyelinating neuropathy caused by mutations in the Myelin Protein Zero gene. It is inherited in an autosomal dominant fashion. So far only a few patients with a focally folded myelin phenotype on nerve biopsy have been shown to have mutations in the Myelin Protein Zero gene. In this report we describe a Polish patient with Charcot-Marie-Tooth type 1B disease. Sural nerve biopsy demonstrated focally folded myelin. Molecular genetic analysis of the coding region of the Myelin Protein Zero gene revealed a novel mutation, Thr65Ala, in exon 2 of the Myelin Protein Zero gene.

Neuroacanthocytosis. Review of literature and case report.

Neuroacanthocytosis is a rare disease of nervous system with multisystem pathology. This review presents clinical syndromes and morphological changes of sporadic and familial forms of neuroacanthocytosis and is illustrated by the case of a 27-year-old man. Progressive extrapyramidal syndrome appeared at the age of 22. Dementia preceded by behavioral changes observed since childhood, was noticed when he was 24 years old. Gross examination of the brain showed atrophy of the brain and caudatum. In microscopic examination most intensive changes were manifested by caudate nucleus atrophy of its head and body, loss of small neurons and extensive astrocytic reaction in dorso-lateral part of the putamen. Within the pallidum similar but less intensive pathological changes were visible. These data are in accordance with those found in literature, but in contrary to the authors who gave attention to spared cerebral cortex which distinguishes neuroacanthocytosis from Huntington's chorea. In the examined case hypocellularity of the cerebral mainly frontal cortex with lamina disorganization but without glial reaction was noted. Moreover, in frontal cortex especially within layer III, differently oriented pyramidal cells its conglomerates and very large neurons were observed. Authors suggest that these alterations are probably manifestations of developmental failures of the cerebral cortex. They concluded that anatomical studies support the possibility that lesions of basal ganglia lead to abnormal intellectual functions.

Coexistence of various vascular malformations within the brain.

Authors present two cases of basilar artery aneurysm accompanied by different development failures of blood vessels. In both cases anomaly in formation of brain base vessels, angioma consisted of different size thin-walled vessels and arterio-venous angioma within brain stem were stated. Besides, conglomerates of abnormal vessels, angiosis within pia matter, diffused lacunar and fetal as well as thin-walled venous vessels were found. Pathological vessels, their conglomerates were present in brain stem, cerebellum and cerebral hemispheres. The variability of vascular malformations seems to point at long-lasting action pathogenic factor during ontogenesis. Authors try to refer particular developmental anomalies to proper stage of ontogenesis.

Paraneoplastic syndrome in the course of lung adenocarcinoma: morphological picture and immunohistochemical analysis of the inflammatory infiltrates and PECAM-1 expression.

We examined sections of brain, spinal cord, spinal roots, and peripheral nerves from a patient with paraneoplastic syndrome in the course of lung adenocarcinoma. Morphological examination showed marked loss of myelin fibers in peripheral nerves, severe brain tissue edema, and paraneoplastic degeneration involving cerebrum and cerebellum with inflammatory components. Inflammatory infiltrates examined immunohistochemically using antibodies against antigens CD 3, CD 4, CD 8, and CD 20 turned out to be composed of cytotoxic T lymphocytes. The expression of platelet-endothelial cell adhesion molecule-1 (PECAM-1) in blood vessels was increased in comparison with control material, which may facilitate transendothelial lymphocyte migration triggering a cascade of biochemical and morphological reactions observed in paraneoplastic syndrome.

[Axonal form of Guillain-Barre syndrome?]. / Aksonalna postac zespolu Guillain-Barré.

Patient, 19 year old man with rapidly developing motor, sensory and autonomic polyneuropathy fulfilling diagnostic criteria for G-B syndrome is presented. Sural nerve biopsy revealed severe axonopathy, however, it seems due to primary demyelinating process.

[Giant-axon polyneuropathy (case report)]. / Polineuropatia z olbrzymimi aksonami (opis przypadku).

In a girl aged 8 years with clinical manifestations of polyneuropathy histological examination of the sural nerve demonstrated segmental distension of axons. The characteristic appearance of her hair, signs of peripheral nervous system damage and morphological findings in the sural nerve made possible the diagnosis of giant-axon polyneuropathy.

[So-called parietal muscular atrophy]. / W sprawie tzw. ciemieniowego zaniku miesni.

A case is reported of a tumour in the parietal area with atrophy of upper extremity muscles but without changes in laboratory investigations.

[Case of hereditary sensory neuropathy with atypical clinical course]. / Przypadek dziedzicznej neuropatii czuciowej o nietypowym obrazie klinicznym.

The authors report cases of hereditary sensory neuropathy of atypical clinical pattern in siblings. Besides evident sensory disturbances signs of peripheral motoneuronal damage and cerebellar signs were present. Electrophysiological and histological investigations in one of these cases confirmed that sensory disturbances were connected with damage to the peripheral sensory neuron.

[Polyneuropathy in the course of Hodgkin's disease: case report]. / Polineuropatia w przebiegu choroby Hodgkina -- opis przypadku.

Polyneuropathy in neoplastic process practically may occur in every stage, before clinical signs, together with clinical signs and in the last period. In some percent of patients polyneuropathy may outstrip manifestation of neoplastic process even for many years. We present a 61-year-old patient in whom signs of polyneuropathy appeared before the signs of essential disease - Hodgkin's disease. Our case confirms the necessity of very careful and precise diagnostics of polyneuropathy with unclear aetiology.

[Electrophysiological abnormalities in acute and chronic inflammatory demyelinating polyneuropathies]. / Zmiany elektrofizjologiczne w ostrych i przewleklych zapalnych polineuropatiach demielinizacyjnych.

Electrophysiologic changes in G-B and CIDP polyneuropathy. Retrospective comparative study of the electrophysiologic changes in 7 cases of GBS and 12 cases of CIDP polyneuropathy were performed. In all cases nerve stimulation data fulfilled the diagnostic electrophysiologic criteria of demyelinated inflammatory polyneuropathy. Our material confirms that electrophysiological investigations are a very important diagnostic tool in inflammatory demyelinating polyneuropathy. However, different electrophysiologic features in individual cases and in the course of the disease cause that nerve stimulation data have no diagnostic value in differentiation between the GBS and CIDP cases.

[Case of probable spino-pontine degeneration]. / Przypadek prawdopodobnego zwyrodnienia rdzeniowo-mostowego.

The reported case illustrated the nosological difficulties in diseases grouped under the term hereditary ataxia.

[Neurosarcoidosis or Guillain-Barre syndrome complicating sarcoidosis]. / Neurosarkoidoza czy zespól Guillain-Barré w przebiegu sarkoidozy?

We described a young male with severe Guillain-Barré syndrome in whom pulmonary sarcoidosis was also detected. Based upon the results of diagnostic procedures (nerve biopsy, CSF examination, electrophysiological study) we postulate that this was a Guillain-Barré syndrome coexisting with sarcoidosis, and not the case of sarcoid neuropathy.

[Motor-sensory hereditary neuropathy. III. Histological changes]. / Ruchowo-czuciowa neuropatia dziedziczna. III. Zmiany histologiczne.

The authors describe the results of histological examinations of the sural nerve in 40 cases of sensorimotor hereditary neuropathy. A comparison of the morphological findings with the values of conduction velocity showed that all cases with "primary demyelination" belonged to the I type of this neuropathy (with conduction velocity under 38 m/sec) while those with axonal changes (and conduction velocity over 38 m/sec) belonged to type II. In 2 cases the degree of demyelination and axonal changes was similar, but the electrophysiological criteria failed to correspond to those of the "intermediate" type. These observations confirmed the validity of the classification of Harding and Thomas, but give no basis for isolation of an "intermediate" group as suggested in the classification of Bradley et al. A progression of demyelination changes was observed with increasing intensity of the pathological process, and frequent coexistence of axonal changes in type I, and possibility of greater damage to the thin myelinated fibres in relation to thick fibres in type II.

[Sensorimotor hereditary neuropathy. IV. Clinical, electrophysiologic and histologic correlations. Summary of studies]. / Ruchowo-czuciowa neuropatia dziedziczna. IV. Korelacje kliniczno-elektrofizjologiczno-histologiczne. podsumowanie badan.

On the basis of a material comprising 53 cases of sensorimotor hereditary neuropathy from 40 families the authors discuss the results of studies on the clinico-electrophysiological-histological correlations. The electrophysiological and histological studies demonstrated the validity of separation of this disease into two types according to the criteria given by Harding and Thomas. No significant differences were found in the clinical manifestations between type I and type II of the disease. In type I the clinical and histological findings were more varied than in type II. No basis was found for isolation of an intermediate type of peroneal muscular atrophy.

[Hereditary motor and sensory neuropathy. I. Principles of classification and clinical picture]. / Ruchowo-czuciowa neuropatia dziedziczna. I. Podstawy klasyfikacji, obraz kliniczny.

The clinical picture was analysed in two types of hereditary motor-sensory neuropathy isolated on the ground of electrophysiological criteria. Type I comprised 34 patients with the conduction velocity in median nerve below 38 m/sec. Type II 19 patients with the conduction velocity above 38 m/sec. The age of onset was similar in both types and cases with onset below the age of 5 years prevailed. The assessment of the clinical picture using a acoring system failed to show any significant differences between type I and type II. Cases of type I shows, however, a considerable variability of the clinical picture and the course of disease process. Cases of type II were more homogeneous.

[Hereditary motor-sensory neuropathy. II. Electrophysiological studies]. / Ruchowo-czuciowa neuropatia dziedziczna. Czesc II. Zmiany elektrofizjologiczne.

Electrophysiological parameters (conduction velocity, distal latency, amplitude of evoked response) were analysed in two types of sensorimotor hereditary neuropathy isolated on the ground of the values of motor conduction velocity in the median nerve which was 38 m/sec. Using this criterion the studied material of 53 cases could be divided into two groups. Group I of 34 cases in which the mean conduction velocity in the median nerve was 16.2 m/sec, and group II of 19 cases had a mean conduction velocity in the median nerve of 50.7 m/sec. The evaluation of the degree of slowing down of conduction in both types showed similar values in individual cases and in families.

[Hereditary neuropathy with liability to pressure palsies caused by 17p11.2 chromosome deletion]. / Dziedziczna neuropatia z nadwrazliwoscia nerwów na ucisk spowodowana delecja w chromosomie 17p11.2.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterised by recurrent mononeuropathies. Electrophysiological studies reveal slowed conduction velocity in peripheral nerves. The main histopathological findings are focal thickenings of myelin-tomaculae. In most cases HNPP is associated with a deletion within PMP-22 (peripheral myelin protein; PMP) gene on chromosome 17p11.2. The gene penetration is almost complete but the expression may be variable. DNA analysis is of practical importance in diagnosing HNPP especially in sporadic cases and also in individuals without clinical and electrophysiological signs of neuropathy. We present the first Polish family with HNPP, in which the genetic defect has been confirmed by DNA analysis.