Mitochondrial disease and stroke.

BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged

Mitochondrial DNA point mutation in the COI gene in a patient with McArdle's disease.

We studied a 57-year-old female patient with clinical and biochemical evidences of McArdle's disease. Her muscle biopsy also revealed signs of mitochondrial proliferation, scattered RRF, and a deficit in complex I of the respiratory chain. Molecular genetic analysis showed that the patient was heterozygous for the most common mutation at codon 49 in the myophosphorylase gene. Mitochondrial DNA analysis of muscle tissue revealed an additional G-to-A transition at nucleotide position 7444 in the cytochrome c oxidase subunit I (COI) gene.

Myophosphorylase deficiency associated with a defect in complex I of the mitochondrial respiratory chain.

We studied a 21-year-old patient with clinical, biochemical and histochemical evidence of myophosphorylase deficiency and unusual repetitive episodes of pigmenturia. His muscle biopsy also revealed morphological signs of mitochondrial proliferation and a defect of complex I of the respiratory chain. His mother had exercise intolerance without myoglobinuria and no histochemical evidence of myophosphorylase deficiency. In muscle, the mother showed some ragged-red fibers, normal respiratory chain levels and a significant residual phosphorylase activity. Molecular genetic analysis revealed that the proband was homozygous for the mutation commonly found in McArdle's disease. The mother, father, and the five siblings were all heterozygous for the same mutation. Mitochondrial DNA analysis of the proband's muscle failed to demonstrate known mutations associated with his clinical pattern. Moreover, we sequenced his tRNA(Leu(UUR)) gene, a hot spot for mutations, showing no abnormality.

[Granulomatous and allergic angiitis (Churg and Strauss). A case report (author's transl)]. / Angiitis granulomatosa y alérgica (Churg y Strauss). A propósito de un caso.

The autopsy findings in a case of granulomatous and allergic angiitis, or Chung and Strauss' disease, are reported. Certain uncommon peculiarities were seen during the course of the disease, such as the presence of multiple lymph nodes presumed from a clinical standpoint to be lymphomas. Its differential diagnosis from other forms of granulomatous vasculitis, especially from those which affect the lungs preferentially or exclusively, is discussed. Special consideration is given to the limited forms of Wegener's disease, which is surprisingly similar morphologically; its more significant differences lie in the clinical and topographic areas, rather than in morphology. The lymph nodes, presumed to be lymphomas from a clinical view-point, are a truly exceptional circumstances in this disease. In the author's opinion the histologic pattern clearly indicates that the etiopathogenesis lies in a congenital or acquired immune disturbance. The recent literature is review, while the present knowledge about the broad and confusing spectrum of these conditions --arteritis, and pulmonary granulomatosis-- is discussed.

[Usefulness of cerebral biopsy in focal cerebral lesions in patients with human immunodeficiency virus infection]. / Utilidad de la biopsia cerebral en las lesiones cerebrales focales en pacientes con infección por el virus de la inmunodeficiencia humana.

Brain mass lesions (BML) occurred in 10% of patients infected by the human immunodeficiency virus (HIV), as expression of severe and sometimes treatable diseases. However, the management of them is not well established. We analyzed, retrospectively, 26 brain biopsies (22 estereotaxic) in patients with HIV infection and BML to know their usefulness and safety. The inclusion criteria were: Failure of the anti-Toxoplasma empirical treatment, atypical scan appearance for toxoplasmosis, or severe neurological picture. Brain biopsy yielded a diagnosis in 19 patients (73.1%): Progressive multifocal leukoencephalopathy (n = 8; 30.8%), primary central nervous system lymphoma (n = 6; 23.1%), mycobacteriosis (n = 2; 7.7%), toxoplasmosis (n = 2; 7.7%), criptococcosis (n = 1), cryptosporidiosis (n = 1) and HIV-encephalitis (n = 1). In one case there was a multiple diagnosis: mycobacteriosis, toxoplasmosis, and lymphoma. Brain biopsy results decided a change in therapy in 65.4%, the resolution or improvement of the neurological process in 30.8%, and the determination of the prognosis in 30.8%. In 8 cases (30.7%) there were biopsy complications, with secondary mortality in one. Brain biopsy of BML in HIV-infected patients is a diagnostic method with a high overall diagnostic rentability and uncommon non reversible complications, offering the possibility to prescribe a specific and potentially curative treatment.

[Chronic demyelinating polyneuropathy associated with multiple sclerosis: a patient with two diseases]. / Polineuropatia crónica desmielinizante asociada a esclerosis múltiple. Un paciente y dos enfermedades.

We studied the clinical, paraclinical and laboratory findings of a patient suffering from multiple sclerosis (MS) with chronic demyelinating polyneuropathy. As well as being a new case of demyelination of the central and peripheral nervous system not normally associated with the presence of antiganglionic antibodies, our patient presented clinical signs distinct from each disease with the characteristic abnormalities of cerebrospinal fluid (CSF) (cytological albumin dissociation at the moment when an outbreak appeared at the peripheral level and an increase in intrathecal secretion when the outbreak was at the central nervous system level). Demyelinating diseases of the central and peripheral nervous systems are a field of great interest in trying to find the antigenic bull's eye for MS.

[Pulmonary tumorlets in POEMS syndrome]. / Tumorlets pulmonares en el síndrome POEMS.

POEMS syndrome is a systemic disease characterized by severe chronic polyneuropathy, organomegaly (adenopathy, and liver enlargement) endocrinopathy, monoclonal peak, sclerotic bone lesions and skin changes. We report on a case of complete POEMS syndrome with peripheral arterial thrombosis and multiple lung tumorlets. No antibodies were found against human nervous tissues or Rhesus monkey on patient serum. This case is the first association described of POEMS syndrome and lung tumorlets.

[Davidenkow syndrome]. / Síndrome de Davidenkow.

A 31-year-old female had since childhood walking difficulties on her right foot. She subsequently developed a right-sided scapuloperoneal amyotrophy with mild distal sensory sings. Nerve conduction velocities and nerve biopsy showed a peripheral neuropathy, and the case was thought to be an example of Davidenkow's syndrome. At the age of 41, the musculature innervated by the right V, VII, XI and XIIth cranial nerves became impaired and this suggested that the lower motor neuron was also involved precluding this picture from inclusion among the Hereditary Motor and Sensory Neuropathies (HMSN) to which Davidenkow's syndrome has been related.

Familial hypertrophic cardiomyopathy and muscle carnitine deficiency.

Five members of the same family, along three generations, presented with hypertrophic cardiomyopathy. Neurological examination, muscle strength, electromyography, and serum creatine kinase were normal. Skeletal muscle biopsy showed abnormal lipid accumulation and carnitine deficiency. In three patients the cardiac symptoms and echocardiographic findings improved after treatment with L-carnitine, 3-4 g daily, and a long-chain fatty-acid-free diet.

Late onset parkinsonian syndrome in Hallervorden-Spatz disease.

Two siblings, from consanguineous parents, developed in their twenties a Parkinsonian syndrome. In the elder, the disease evolved for 13 years and the necropsic study was diagnostic of Hallervorden-Spatz disease. The younger sibling is severely affected after 12 years of the disorder. Several CT and one MR studies done in this patient during the last 4 years have been normal. Ultrastructural studies of the bone marrow histiocytes and blood lymphocytes disclosed peculiar inclusions. Bromocriptine in low doses proved to be a beneficial therapy for this patient.

[Non-paraneoplastic polioencephalomyelitis]. / Polioencefalomielitis no paraneoplásica.

A 60-year-old male presented with cerebellar ataxia and ocular flutter which disappeared after ten months of evolution. The patient later had three other different bouts which caused cerebral, brainstem and polyradiculoneuritis-like symptomatology. The disease evolved in 20 months and at necropsy a primary polioencephalomyelitis was found. The remitting and relapsing course of the disease is better explained by an autoimmune-mediated lesion.

[Multifocal demyelinating neuropathy with persistent conduction blocks and continuous muscular activity]. / Neuropatía desmielinizante multifocal con bloqueos de conducción persistentes y actividad muscular continua.

A patient developed an initially asymmetric sensory-motor neuropathy, with definite predominance in upper limbs. The examination also disclosed a markedly impaired muscle relaxation. The neurophysiological study showed conduction blocks with continuous muscle activity consisting of myokymias fasciculations and muscle cramps which disappeared after the anesthetic block of the distal nerve segments. In the sural nerve biopsy significant abnormalities were not found. After prednisone and carbamazepine therapy in usual doses the symptoms reverted and the conduction blocks persisted. Neuropathy with persistent conduction blocks is an uncommon disease which exceptionally results in a clinically apparent syndrome of continuous muscle activity. Its recognition is important, as symptoms can disappear after correct therapy.

Continuous muscle activity and distal spinal muscular atrophy.

A young man presented with myokymias, cramp-like difficulty in muscle relaxation and peroneal atrophy. EMG studies revealed continuous muscle activity (CMA) manifested as grouped potentials and high frequency discharges. Sensory nerve conduction studies and sural nerve biopsy gave normal results, and he was thought to suffer from distal spinal muscular atrophy with CMA. This association suggests that the lower motor neuron may have an important role in the generation of the continuous muscle activity.

[Recurrent familial brachial plexopathy as the only clinical expression of neuropathy with susceptibility to pressure]. / Plexopatía braquial recurrente familiar como única expresión clínica de una neuropatía con susceptibilidad a la presión.

We report a family with hereditary neuropathy with liability to pressure palsies (HNPP) and chromosome 17p11.2 deletion. This family exhibits a peculiar phenotype consisting in recurrent brachial plexopathy episodes. This phenotype has to be distinguished from hereditary neuralgic amyotrophy on clinical grounds. Although the incidence of brachial plexopathy on HNPP is relatively high it is unusual as the sole symptom of the disease. It is noteworthy that in the six published families with this peculiar phenotype most of the acute episodes became evident after sleep. A greater liability of the plexus and a greater vulnerability to mechanical factors during sleep hours are the suggested mechanisms to explain this rare clinical onset. Recurrent painless brachial plexopathy when associated to generalized conduction abnormalities should suggest a HNPP.

[Congenital myopathy with cores and nemaline rods in one family]. / Miopatía congénita con cores y bastones nemalínicos en la misma familia. Asociación a un síndrome del túnel carpiano.

We present a mother and 2 children with congenital myopathy whose clinical signs were facial paresis in all three, and mild involvement of the lower extremities in the mother and one son. All three presented skeletal abnormalities, hypertelorism, arched palate, retraction of the Achilles tendon or short neck. Symptoms were not progressive and muscle biopsies showed central cores and nemaline rods in the mother and only nemaline rods in the 2 sons. The mother also suffered carpal tunnel syndrome, as had other members of the family as the result of autosomal dominant inheritance.

Dialysis myopathy. Report of 13 cases.

Thirteen patients hemodialyzed for chronic renal insufficiency developed progressive paresis of the proximal musculature. Biopsies of the deltoid muscles of ten patients showed selective atrophy of type 2 fibers, the cause of which seems to be related to the osteomalacia present in those patients. Purification of the water for dialysis prior to the procedure prevents the muscle alteration: however, once the lesion is established only renal transplant will permit recovery of the muscle strength of the patient.

[Complex I (NADH coenzyme-Q-reductase) deficiency, MELAS syndrome and hypertrophic cardiomyopathy]. / Déficit de complejo I (NADH coenzima-Q-reductasa), síndrome MELAS y miocardiopatía hipertrófica.

A 24-year-old male had a deficiency of the complex I (NADH coenzyme-Q-reductase) of the mitochondrial respiratory chain, which clinically presented as a mitochondrial encephalomyopathy, with lactic acidosis and stroke-like episodes (MELAS syndrome). The encephalopathic episodes were preceded by migraine and were characterized by focal deficit signs, motor partial seizures and hypodense areas in the CT scan. An echocardiographic diagnosis of hypertrophic cardiomyopathy without intracavitary thrombi was made. It is suggested that hypertrophic cardiomyopathy is caused by the mitochondrial abnormalities that have been reported in the myocardium, and that migraine and cerebral infarctions are associated with abnormalities in the mitochondria from the endothelium and smooth muscle fibres of the cerebral small arteries and arterioles.

[Adult onset mitochondrial myopathy without ophthalmoplegia. Four cases attributable to complex III and IV deficits in the respiratory chain]. / Miopatía mitocondrial de inicio en la edad adulta sin oftalmoplejía. Presentación de 4 casos por déficit de complejos III y IV de la cadena respiratoria.

Four adults with proximal myopathy of mitochondrial origin but no ocular involvement are presented. Biochemical analysis showed combined complex III and IV deficits in the respiratory chain in all cases, suggesting an apparent correlation between clinical phenotype and biochemical findings. Mitochondrial DNA analysis of muscle from 1 patient failed to detect either large-scale deletion or point mutations at position 3243 of tRNA(Leu(UUR)) or at 8344 of tRNA(Lys). The tissue specificity of the disease and the absence of family history suggest that a mutation in a nuclear DNA gene encoding a specific subunit of muscle could underlie this disease.