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Gérard Said

Publications and source records attributed to Gérard Said.

11 recordsLinked to original sources
PubMed2003

Neuropsychiatric disturbances in presumed late-onset cobalamin C disease.

BACKGROUND: Combined methylmalonic aciduria and homocystinuria cobalamin C type (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired intracellular synthesis of the 2 active forms of vitamin B12 (cobalamin), namely, adenosylcobalamin and methylcobalamin, that results in increased levels of methylmalonic acid and homocysteine in the blood and urine. Most patients present in the first year of life with systemic, hematological, and neurological abnormalities. Late-onset forms are rare and had not been comprehensively characterized. They could be easily misdiagnosed. OBJECTIVE: To describe clinical and biochemical features of the disease in 2 siblings affected with presumed late-onset cobalamin C disease. DESIGN: Case report and review of the literature. SETTING: Neurological intensive care unit of a university hospital. OBSERVATION: We describe 2 patients with neurological deterioration due to presumed cobalamin C disease. A 16-year-old girl was initially seen with psychosis and severe progressive neuropathy requiring mechanical ventilatory support and her 24-year-old sister had a 2-year disease course of subacute combined degeneration of the spinal cord. A metabolic workup displayed increased methylmalonic acid levels, severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was then confirmed by demonstration of impaired synthesis of adenosylcobalamin and methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus-infected lymphocytes. Under specific treatment the younger sister's condition dramatically improved. CONCLUSIONS: Although complementation studies have not been conducted, it is most likely these patients had cobalamin C disease. This study emphasizes the possibility of late-onset disease with purely neurological manifestations. Left untreated, this treatable condition can lead to death or irreversible damage to the nervous system. Screening for intracellular vitamin B12 dysmetabolism should, therefore, be considered in the investigation of adults with unexplained neurological disease, particularly when they are initially seen with a clinical picture suggestive of vitamin B12 deficiency.

Adolescent↗
PubMed2003

Inflammatory vasculopathy in multifocal diabetic neuropathy.

Besides the common distal symmetrical sensory-motor polyneuropathy (DSP) that is often associated with autonomic dysfunction, diabetic patients may develop multifocal sensory-motor deficits (MDN) secondary to roots, plexus and nerve trunk involvement. Nerve ischaemia has been suggested as a common mechanism for the different patterns of diabetic neuropathies, yet the important clinical differences that exist between DSP and MDN suggest concurrent factors. In order to learn more on the subject, we prospectively studied 22 consecutive diabetic patients with MDN, for which other causes of neuropathy were excluded by appropriate investigations, including biopsy of a recently affected sensory nerve. Three patients had a relapsing course, and the others an unremitting subacute-progressive course. Painful MDN progressed over 2-12 months. The neurological deficit predominated in distal lower limbs which were involved in all patients, unilaterally in seven, bilaterally in the others, with an asynchronous onset in most cases. In addition, a proximal deficit of the lower limbs was present on one side in seven patients, and on both sides in six. Thoracic radiculoneuropathy was present bilaterally in two patients, and unilaterally in one. The ulnar nerve was involved in one patient, and the radial nerve in two. The CSF protein ranged from 0.40 to 3.55 g/l; mean: 0.87 g/l. Electrophysiological testing showed severe, multifocal, axonal nerve lesions in all cases. Asymmetrical axonal lesions were found in all nerve specimens. The mean density of myelinated axons was reduced to 1340 +/- 1070 per mm(2) of endoneurial area versus 8370 +/- 706 myelinated fibres/mm(2) in controls. The mean density of unmyelinated fibres was reduced to 5095 +/- 6875 per mm(2) (extremes: 0-26 600). On teased fibre preparations, 34 +/- 31% of the fibres were at different stages of axonal degeneration (extremes 0-99%); 7 +/- 6% of the fibres showed segmental demyelination or remyelination. Necrotizing vasculitis of perineurial and endoneurial blood vessels were found in six patients. Endoneurial seepage of red cells was present in 11 specimens, and endoneurial haemorrhage in five. Ferric iron deposits that characterize previous bleeding were found in seven patients, including two who had no red cells in the endoneurium. Perivascular mononuclear cell infiltrates were present in the nerve specimens of 21 out of 22 patients, prominently in four patients. In comparison, nerve biopsy specimens of 30 patients with severe distal symmetrical diabetic polyneuropathy showed mild epineurial mononuclear cell infiltrate in one patient and endoneurial seepage of red cells in another. We conclude that MDN is related to pre-capillary blood vessel involvement in elderly diabetic patients with a secondary inflammatory response.

Action Potentials↗
PubMed2003

Familial amyloid polyneuropathy: mechanisms leading to nerve degeneration.

Familial amyloid polyneuropathy (FAP) manifests itself as a fiber-length-dependent polyneuropathy predominantly affecting sensory and autonomic nervous systems. Endoneurial amyloid deposits can be noxious to nerve fibers in several ways including mechanical and toxic effects on nerve fibers, and impairment of blood supply. On teased fiber preparations, a mixture of axonal degeneration and a lower proportion of segmental demyelination is observed. Within a few years of the first symptoms there is a near complete disappearance of myelinated and unmyelinated nerve fibers in the nerve samples taken by biopsy. On teased fiber preparations, amyloid deposits induce distortion, demyelination and eventually distal axonal degeneration of neighboring nerve fibers. This "mechanical" effect is associated with a "toxic" effect of amyloid fibrils leading to the disappearance of the basal lamina of Schwann cells, followed by death, presumably by apoptosis. Amyloid deposits often cluster around endoneurial blood vessels, and even invade their wall with subsequent occlusion of endoneurial vessels themselves.

Amyloid↗
PubMed2002

Matrix metalloproteinases-9 and -2 in secondary vasculitic neuropathies.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endoproteinases that play an important role in inflammation and tissue degradation. MMP-9 and MMP-2 are gelatinases that have been implicated in the degradation of the blood-brain or blood-nerve barrier. We present an immunohistochemical study on 11 nerve biopsy samples of inflammatory and non-inflammatory polyneuropathies. Perineurium and endothelium were positive for MMP-2 in all tissue sections. In addition, there was a specific up-regulation of MMP-2 in stromal cells of chronic inflammatory demyelinating polyneuropathy (CIDP) and even more in vasculitic neuropathies. MMP-9-positive cells were detected in vessel walls, infiltrates, epineurium and endoneurium of vasculitic neuropathies. In CIDP, MMP-9-positive cells were prominent in vessel walls. Only a few MMP-9-positive cells were detected in noninflammatory controls in blood vessels and adhering to vessel walls. Double staining indicated that the infiltrating cells were T cells and macrophages. Our findings suggest that MMP-9 plays an important role in inflammatory peripheral neuropathy probably as means for inflammatory cell invasion.

Adult↗
PubMed2002

Regeneration of primary sensory axons into the adult rat spinal cord via a peripheral nerve graft bridging the lumbar dorsal roots to the dorsal column.

This study investigated the feasibility of using a peripheral nerve autograft (NAG) to promote and guide regeneration of sensory axons from the caudal lumbar dorsal roots to the rostral dorsal column following a lower thoracic cordotomy in adult rats. After a left hemicordotomy at the T13 vertebra level and ipsilateral L3 and L4 rhizotomies, a peripheral NAG (peroneal nerve) was connected to the distal roots stumps, then implanted into the left dorsal column 10 mm rostral to hemicordotomy site (n = 12). After surgery, all animals of the experimental group experienced complete anesthesia in their left hindlimb. Three months later, a slight response to nociceptive stimulation reappeared in L3 and/or L4 dermatomes in 6 of the 12 experimental animals. None of these animals exhibited self-mutilation. Nine months after surgery, we performed retrograde tracing studies by injecting horseradish peroxidase (HRP) into the left dorsal column 30 mm rostral to the NAG implantation site. In eight animals, we found HRP-stained neurons in the left L3 and/or L4 dorsal root ganglia (DRG). The mean number of HRP-stained neurons per DRG was 71 +/- 92 (range 2-259). In control groups, no HRP-stained neurons were found in L3 or L4 DRG. Histological analysis of the NAG showed evidence of axonal regeneration in all 8 animals with positive retrograde labeling of DRG neurons. However, we did not find a statistical correlation between the number of HRP-stained neurons and the degree of sensory recovery. This study demonstrates that an NAG joining dorsal roots to the dorsal column, thus shunting the original CNS-PNS junction, can support regeneration of central axons from DRG primary sensory neurons into the dorsal column over distances of at least 30 mm despite the inhibitory influence of the CNS white matter.

Age Factors↗
PubMed2002

Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy.

Dejerine-Sottas disease (DSD) was originally described as a hypertrophic polyneuropathy characterized by onset in infancy or early childhood in patients born to unaffected parents. The clinical features included distal sensory changes with ataxia; pes cavus, at times with kyphoscoliosis; motor deficit and atrophy predominating in the distal lower limbs and progressing toward the proximal limbs following a length-dependent pattern; palpable nerve hypertrophy; and Argyll-Robertson pupils. The morphological hallmark was the extensive nerve and root hypertrophy associated with demyelination-remyelination of surviving, originally myelinated axons and profuse Schwann-cell proliferation forming onion bulbs. Wide variations in clinical manifestations of chronic demyelinating polyneuropathies of early onset in children born to unaffected parents have now been reported, with only some of the characteristics required in the original study, and at least seven genes encoding the myelin proteins P0, PMP22, the transcriptional factor EGR2, and others have been implicated. Thus, DSD is now a component of the hereditary demyelinating polyneuropathies of infancy that also include subsets of the recently individualized CMT4 neuropathies. The presumed recessive transmission of patients with DSD should be confirmed by molecular genetic analysis, which is still negative in a significant proportion of patients. The nerve biopsy can be useful in patients in whom genealogical or DNA abnormalities in favor of a genetic disorder are missing, because in a few patients with a progressive or relapsing course the diagnosis of early-onset chronic inflammatory demyelinating polyneuropathy must be considered.

Axons↗
PubMed2002

Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients.

We have reviewed the clinical and pathological data of a series of 100 consecutive diabetic patients with symptomatic neuropathy in order to learn more about the causes of neuropathy in this population and on the signs and symptoms that could suggest another cause than diabetes in this setting. After diagnostic procedures, patients were assigned one (at most two) of a final total of 18 different causes of neuropathy. Diabetes accounted for 74 % of the neuropathies in the whole group of patients and for 79 % of those with a fiber length dependent pattern of neuropathy. One third of patients had a neuropathy unrelated to diabetes. As a group, 71 % of the patients presented either a length dependent diabetic polyneuropathy (LDDP) or a proximal diabetic neuropathy (PDN). The LDDP group was biased towards more severely affected patients owing to our specialization. Conversely, most patients with proximal diabetic neuropathy had usual features. Chronic inflammatory demyelinating neuropathy that was diagnosed in 9 % of the patients was the most common non-diabetic cause of neuropathy in this population. We conclude that a short interval between diagnosis of diabetes and the onset of the neuropathy, early motor deficit, markedly asymmetrical deficit and generalized areflexia, which are all uncommon in the LDDP, argue in favor of a non diabetic origin of the neuropathy and should lead to further investigation.

Adult↗
PubMed2002

Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients.

Peripheral neuropathy is a rare, yet treatable manifestation of sarcoidosis, a multisystem disorder characterized by the presence of non-caseating granulomas that are seldom found in nerve biopsy specimens. In order to learn more about the subject, we reviewed our clinical and pathological findings in a series of 11 patients (six men and five women aged 26-83 years) with symptomatic neuropathy associated with characteristic granulomas in nerve biopsy specimens. Only two patients were known to have sarcoidosis before the occurrence of the neuropathy. The neuropathy was focal or multifocal in six patients, including one with a multifocal neuropathy associated with conduction blocks, and one with a multifocal axonal motor deficit. Four patients had a distal symmetrical deficit and one patient had a Guillain-Barré-like syndrome with facial diplegia and respiratory failure. Serum angiotensin-converting enzyme concentration was elevated in only two patients. Epineurial granulomas and perineuritis were present in all nerve specimens. The inflammatory infiltrates invaded the endoneurium, following connective tissue septae and blood vessels, in five patients. Multinucleated giant cells were found in eight patients and necrotizing vasculitis in seven. Inflammatory lesions were associated with variable, asymmetrical involvement of nerve fascicles and axon loss. A muscle specimen was sampled during the same procedure in 10 patients. It showed inflammatory infiltrates and granulomas in nine patients and necrotizing vasculitis in two. Immunolabelling showed a mixed inflammatory infiltrate of T cells (predominantly CD4+ cells) and macrophages, in keeping with a delayed hypersensitivity reaction. In addition to nerve involvement, all patients had at least one other tissue or organ affected, including muscle in nine patients, lungs and/or intrathoracic lymph nodes in eight, skin in three, arthritis in two, and peripheral lymph nodes, stomach and eye in one patient each. Most patients improved on corticosteroids. Two patients remain free of symptoms after 7 years. Severe side-effects of long-term treatment with corticosteroids occurred in two patients, leading to death in one. This study illustrates the wide range of clinical manifestations of sarcoid neuropathy and the frequent association of granulomatous inflammatory infiltrates with necrotizing vasculitis and with silent or symptomatic involvement of other organs.

Adult↗