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.

Charcot-Marie-Tooth type 4F disease caused by S399fsx410 mutation in the PRX gene.

Charcot-Marie-Tooth type 4F disease (CMT4F) is an autosomal recessive neuropathy caused by mutations in the PRX gene. To date, only seven mutations have been identified in the PRX gene. In this study, the authors report a novel S399fsX410 mutation in the PRX gene and its effects at the protein level, which was identified in an 8-year-old patient with early-onset CMT disease.

Autosomal recessive axonal form of Charcot-Marie-Tooth Disease caused by compound heterozygous 3'-splice site and Ser130Cys mutation in the GDAP1 gene.

A recessive demyelinating subtype of Charcot-Marie-Tooth disease called CMT4 is a heterogeneous group of disorders. A relatively frequent form of recessive CMT (CMT4 A) has been mapped to the chromosome 8 q21 and shown to be caused by mutations in the ganglioside-induced differentiation protein 1 (GDAP1) gene. Twenty mutations in the GDAP1 gene have been reported in patients suffering from the axonal and demyelinating forms of CMT disease. In this study we report two novel mutations in the GDAP1 gene in a patient suffering from CMT2 disease and whose parents were asymptomatic carriers of a Ser130Cys and 3'-splice site (311-1G > A) mutation, respectively.

A novel MPZ gene mutation in congenital neuropathy with hypomyelination.

Congenital hypomyelinating neuropathy (CHN; MIM# 605253) is a severe neuropathy with early infancy onset inherited as an autosomal dominant or recessive trait. Sural nerve biopsy shows a characteristic picture of nonmyelinated and poorly myelinated axons with basal lamina onion bulbs and lack of myelin breakdown products. Several mutations in the MTMR2, PMP22, EGR2, and MPZ genes have been found in patients with CHN. The authors describe the clinical and morphologic features of a patient with CHN and the identification of a novel Thr124Lys mutation in the MPZ gene.

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.

Focally folded myelin in Charcot-Marie-Tooth type 1B disease is associated with Asn131Lys mutation in myelin protein zero gene: short report.

Charcot-Marie-Tooth disease type 1B (CMT1B) is a demyelinating neuropathy inherited as an autosomal dominant trait. The majority of CMT1B cases are caused by mutations in the myelin protein zero (P0) gene (MPZ). Only a few mutations in MPZ gene have been reported to be associated with focally folded myelin sheaths. We have studied five patients from one family with five generations, affected by CMT1B disease. The morphological studies of sural nerve biopsy performed in the proband revealed fibers with focally folded myelin. DNA sequencing analysis showed the Asn131Lys mutation in the MPZ gene in three members of the affected family.

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.

[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.

[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.

Familial inclusion body myopathy with desmin storage.

We report two adult familial cases of inclusion body myopathy (IBM) with desmin storage in skeletal muscle. Clinically, both patients presented late-onset, progressive, symmetrical, both proximal and distal muscle weakness. Muscle biopsy findings were identical in both cases and consisted of marked variability in fiber size, increased number of central nuclei and vacuolation involving 10% of fibers. Single or multiple vacuoles were located subsarcolemmally or in the center, and were rimmed by basophilic material. At the ultrastructural level, tubulofilamentous nuclear and cytoplasmic inclusions of 16-21 nm in diameter were frequently observed. In addition, large subsarcolemmal and central deposits composed of electron-dense granular material were present in many fibers. Immunocytochemistry revealed staining for desmin, vimentin and ubiquitin within both inclusions and vacuolated fibers. Possible structural and functional associations between these two types of muscle changes remain unclear. They may either represent two coexistent disease processes or merely reflect an abnormal form of muscle fiber degradation, with unidentifiable specificity.

[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.

[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.

[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.

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.

[Diagnostic yield of electrophysiological and immunological studies in inflammatory myopathies]. / Zastosowanie badan elektrofizjologicznych i immunologicznych do diagnostyki miopatii w chorobach tkanki lacznej.

The aim of the study was to estimate the value of the immune markers in defining distinct subsets of inflammatory myopathies. The series of 76 patients was divided, on the basis of the clinical data, into 5 groups (polymyositis (PM), dermatomyositis (DM), scleromyositis (Scm), mixed connective tissue disease (MCTD), unclassified). In all cases detailed clinical, electrophysiological (concentric needle electromyography (CNEMG) and skin sympathetic response (SSR)) were performed as well as immunologic studies: the anti Mi-2, anti RNP, PM-Scl, Jo-1. The findings indicate that immune markers have a diagnostic value in differentiating the defined subsets of patients different in respect of course, prognosis and therapeutic indications. The authors stressed the value of the Jo-1 antibody in detecting the subset of polymyositis with coexisting interstitial lung disease. Electrophysiological data do not differentiate the groups of patients with different clinical syndrome and different immune markers. EMG results seem however to be useful in monitoring the course of the disease and response to the therapy.

Morphological changes in the peripheral nervous system in the case of congenital malformations of the spinal cord.

A 21-year-old oligophrenic man developed after upper respiratory tract infection, quadriplegia with sphincter and respiratory disturbances. Lumbar punction revealed subarachnoid bleeding and elevated cerebrospinal protein level. Guillain-Barré syndrome and subarachnoid hemorrhage were diagnosed. At autopsy intraspinal angioma (C2-D6) and diastematomyelia (D11-lumbar segments) were found. Beside, intraspinal hemorrhage was present. Morphological examination of posterior and anterior spinal roots as well as peripheral nerves was done. Spheroids, axonal degeneration and prominent loss of myelinated fibers were observed in the proximal parts of the spinal roots. Axonal degeneration of myelinated fibers and regenerated fibers were noted in the distal parts of spinal roots and in peripheral nerves. Abnormal, fetal-like vessels were present in the spinal roots. Two mechanisms of acute and chronic changes (transneuronal and Wallerian degeneration) are discussed.

Chronic progressive axonal polyneuropathy simulating Guillain-Barré syndrome.

Six cases of chronic progressive and/or relapsing polyneuropathy are reported. All cases were idiopathic at the beginning of observation. Electrophysiological examination and biopsy of sural nerve in all cases as well as autopsy of spinal roots S1 in case 6 showed loss of fibers and axonal degeneration of myelinated fibers but neither active demyelination nor inflammatory cells were observed. Chronic progressive or relapsing idiopathic axonal polyneuropathy appear to be a distinct entity different from GBS. The term "axonal GBS" seems to be questionable.

Inclusion body myositis (IBM). Morphological study.

Among the chronic idiopathic inflammatory myopathies inclusion body myositis (IBM) has emerged as a clinicopathologic variant. Slowly progressive weakness of the distal and the proximal muscle groups, the presence of rimmed vacuoles with basophilic granules as well as 15-18-nm filamentous inclusions in affected muscle confirm the clinical and histopathological distinction between inclusion body myositis and chronic polymyositis.