RESUMO
Inherited neuropathies are a heterogeneous group of slowly progressive disorders affecting either motor, sensory, and/or autonomic nerves. Peripheral neuropathy may be the major component of a disease such as Charcot-Marie-Tooth disease or a feature of a more complex multisystemic disease involving the central nervous system and other organs. The goal of this review is to provide the clinical clues orientating the genetic diagnosis in a patient with inherited peripheral neuropathy. This review focuses on primary inherited neuropathies, amyloidosis, inherited metabolic diseases, while detailing clinical, neurophysiological and potential treatment of these diseases.
Assuntos
Doença de Charcot-Marie-Tooth , Neuropatia Hereditária Motora e Sensorial , Humanos , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genéticaRESUMO
Treatment strategies in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) must be adapted on a case-to-case basis. Validated and reproducible tools for monitoring treatment response are required at diagnosis, when initiating treatment and throughout follow-up. A task force of French neurologists, experts in neuromuscular disease reference centers, was assembled to provide expert advice on the management of typical CIDP with intravenous immunoglobulins (Ig), and to harmonize treatment practices in public and private hospitals. The task force also referred to the practical experience of treating CIDP with Ig at the diagnostic, induction and follow-up stages, including the assessment and management of Ig dependence, and following the recommendations of the French health agency.
Assuntos
Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Prova Pericial , Imunoglobulinas Intravenosas/uso terapêutico , França/epidemiologiaRESUMO
Mitochondrial diseases are a heterogeneous group of pathologies, caused by missense mutations, sporadic large-scale deletions of mitochondrial DNA (mtDNA) or mutations of nuclear maintenance genes. We report the case of a patient in whom extended muscle pathology, biochemical and genetic mtDNA analyses have proven to be essential to elucidate a unique asymmetrical myopathic presentation. From the age of 34 years on, the patient has presented with oculomotor disorders, right facial peripheral palsy and predominantly left upper limb muscle weakness and atrophy. By contrast, he displayed no motor weakness on the right hemi-body, and no sensory symptoms, cerebellar syndrome, hypoacusis, or parkinsonism. Cardiac function was normal. CK levels were elevated (671 UI/L). Electroneuromyography (ENMG) and muscle MRI showed diffuse myogenic alterations, more pronounced on the left side muscles. Biopsy of the left deltoid muscle showed multiple mitochondrial defects, whereas in the right deltoid, mitochondrial defects were much less marked. Extended mitochondrial biochemical and molecular workup revealed a unique mtDNA deletion, with a 63.4% heteroplasmy load in the left deltoid, versus 8.1% in the right one. This case demonstrates that, in mitochondrial myopathies, heteroplasmy levels may drastically vary for the same type of muscle, rising the hypothesis of a new pathophysiological mechanism explaining asymmetry in hereditary myopathies.
Assuntos
Heteroplasmia , Miopatias Mitocondriais , Masculino , Humanos , Adulto , Miopatias Mitocondriais/patologia , DNA Mitocondrial/genética , Atrofia Muscular/patologia , Músculos/patologiaRESUMO
A 40-year-old woman presented with bilateral juvenile cataract, tendinous xanthomas, intellectual deterioration, spastic tetraparesis, proprioceptive deficit and parkinsonian syndrome. A younger sister's clinical picture differed by the absence of xanthomas and the presence of a cerebellar syndrome. The diagnosis of cerebrotendinous xanthomatosis was confirmed by a high concentration of plasma cholestanol and by urinary chromatography. Magnetic resonance imaging displayed some abnormalities in the hemispheric and cerebellar white matter. Under chenodesoxycholic therapy the biological abnormalities decreased while the clinical disturbances were unchanged.
Assuntos
Tendão do Calcâneo , Encefalopatias Metabólicas/diagnóstico , Catarata/genética , Imageamento por Ressonância Magnética , Xantomatose/genética , Adulto , Atrofia , Encéfalo/patologia , Encefalopatias Metabólicas/genética , Catarata/diagnóstico , Ácido Quenodesoxicólico/uso terapêutico , Colestanol/análise , Feminino , Humanos , Linhagem , Xantomatose/diagnóstico , Xantomatose/tratamento farmacológicoRESUMO
The only etiologic factor retained in 11 patients with sensory or sensory-motor neuropathy was almitrine therapy. In one patient there was in addition an optic neuropathy. The reduction in visual acuity in this patient coincided with the onset of the sensory-motor neuropathy of lower limbs after treatment with 100 mg/day of almitrine over a 2-year period. No other metabolic, inflammatory, toxic, vascular or immunologic cause was found. There was a moderate chronic respiratory insufficiency. Visual recuperation started one month after the arrest of almitrine treatment and was satisfactory 7 months later. The other 10 patients had neuropathy of limbs without visual disorders. Neuromuscular biopsy in one case showed lesions to be of the axonal type.
Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Piperazinas/efeitos adversos , Idoso , Almitrina , Axônios/ultraestrutura , Eletrofisiologia , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Perna (Membro)/inervação , Masculino , Pessoa de Meia-Idade , Neurite Óptica/induzido quimicamente , Doenças do Sistema Nervoso Periférico/patologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Visão Ocular/efeitos dos fármacosRESUMO
A 22-year old man had spastic paraparesis and cerebellar syndrome of 5 months duration. CSF showed lymphocytosis, elevated protein content, hypoglycorachia, hypochlorurachia and oligoclonal banding. CT scan and MRI were normal. Extensive laboratory procedures disclosed no bacterial, viral, fungic, parasitic or inflammatory disease. Anti-Borrelia burgdorferi antibodies were present in blood (1/4000) and in CSF (1/1024). With antibiotics (penicillin G 20 millions units per day for 10 days, followed by latamoxef 1.5 g per day for 3 months) and prednisone (50 mg per day for 2 months), the cerebellar signs disappeared, the paraparesis improved and the CSF abnormalities disappeared; blood and CSF anti-Borrelia antibody levels decreased. This case is an example of a severe form of CNS impairment by Borrelia burgdorferi. In Europe, most reports show progressive para- or tetraparesis with, sometimes, intellectual, cerebellar or cranial nerve impairment. In some cases, the signs are less diffuse or more acute. Lymphocytic meningitis is present with hyperalbuminorachia and oligoclonal banding; hypoglycorachia is mentioned in only one other report. Diagnosis is made by high blood and CSF antibody titers and demonstration of local synthesis. As in syphilis, borrelian meningoencephalomyelitis could be the third stage of the disease. Its treatment, often disappointing, consists of antibiotics (penicillin G or latamoxef) and in some cases corticosteroids.