Distal myasthenia gravis and sensory neuronopathy with anti-50 kDa antibody mimicking sensory-motor neuropathy.
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Aged↗
Biomedical subjects
A Lugaresi
Publications and source records attributed to A Lugaresi.
Chronic progressive steroid responsive axonal polyneuropathy: a CIDP vaariant or a primary axonal disorder?
Five patients presented with chronic,, progressive, predominantly motor polyneuropathy. CSF protein content was increased in 4 patients. Motor conduction velocities and EMG were consistent with axonal involvement. Sural nerve conductions were normal in all cases and sural nerve biopsy performed in 1 patient was normal. Serum antibodies to GM1, GD1a, GD1b, and GM2 were negative. All patients improved after steroid treatment and 3 completely recovered. Because of therapeutic implications it is important to differentiate these patients from those with chronic idiopathic axonal neuropathies. It is unclear whether this is a primary axonal, probably immune-mediated, polyneuropathy, or whether it represents one extreme of the chronic inflammatory demyelinating polyradiculoneuropathy spectrum characterized by severe axonal loss. We suggest that the term "chronic inflammatory polyneuropathy," encompassing cases from pure demyelinating to pure axonal neuropathies responsive to steroids, should be reinstated and that, like in Guillain-Barré syndrome, different subtypes should be individuated.
Adolescent↗
Central alveolar hypoventilation (Ondine's curse) treated with negative pressure ventilation.
A 22 year old woman with central alveolar hypoventilation (CAH) underwent repeated nocturnal polysomnographic recordings to assess the efficacy of negative pressure ventilation (NPV) administered by pneumowrap. The NPV successfully prevented hypoxia during most of the recording time; however, a sudden severe hypoxic episode not related to an apnoea occurred during a recording night with NPV. This made home use advisable together with an ear oximeter fitted with an alarm.
Adult↗
Abnormal brain and muscle energy metabolism shown by 31P-MRS in familial hemiplegic migraine.
Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder of unknown pathogenesis characterized by migraine and transitory hemiplegic attacks. We describe a kindred fulfilling the diagnostic criteria for FHM in which: (1) brain phosphorus magnetic resonance spectroscopy (31P-MRS) showed a reduced phosphocreatine content accompanied by high [ADP], high percentage of V/Vmax of ATP biosynthesis and decreased phosphorylation potential; (2) muscle 31P-MRS showed a reduced rate of phosphocreatine recovery after exercise; (3) blood lactate was increased after effort; (4) muscle biopsy showed, in one patient, rare ragged red fibers succinate-dehydrogenase positive and cytochrome c oxidase negative; (5) genetic analysis of muscle mitochondrial DNA did not show any of the two point mutations in the tRNA(Leu(UUR)) associated with the MELAS syndrome (Mitochondrial myopathy, Encephalopathy with Lactic Acidosis and Stroke-like episodes). The defective energy metabolism of brain and muscle found in this pedigree suggests a multisystemic disorder of mitochondrial function in this FHM pedigree.
Adolescent↗
Benign monomelic amyotrophy of lower limb: a rare entity with a characteristic muscular CT.
Six patients presented with amyotrophy confined to a single lower limb and characterized by insidious onset, slow progression and later stabilization. Wasting was out of proportion with disability and there were no sensory, pyramidal tract or bulbar signs. All cases were sporadic, and there was no history of poliomyelitis. CK, anti-ganglioside antibodies, motor and sensory conductions were normal. Quantitative EMG and muscle biopsy revealed neurogenic features also in clinically unaffected limbs. Muscular CT showed selective or predominant, asymmetrical involvement of posterior leg muscles and caput longus of biceps femoris. Monomelic amyotrophy of lower limb is a clinically localized variant of spinal muscular atrophy with a particularly benign course. Although in the early stage there are no clinical or laboratory findings which allow differential diagnosis with other motor neuron diseases, the history of an amyotrophy clinically localized for more than 3 years to a lower single limb and the characteristic muscular CT pattern suggest the diagnosis since the first observation and indicate a favorable prognosis.
Adult↗
Hand dystonia secondary to cervical demyelinating lesion.
Dystonia is generally considered a disease of basal ganglia. We report two patients with definite MS who acutely developed hand dystonia and athetoid movements. In both patients: 1) dystonia was electrophysiologically demonstrated by lack of reciprocal inhibition between antagonistic forearm muscles; 2) SEP from median nerve stimulation showed delayed cervical N13 and absent frontal and parietal components; 3) the long latency response after stimulation of median nerve of the affected hand was absent or delayed; 4) MRI showed lesions in the posterolateral cervical spine but no involvement of basal ganglia and thalami. We think that, in these cases, dystonia and athetoid movements could be ascribed respectively to the involvement of descending pathways regulating reciprocal inhibition of motoneurons and to the involvement of large diameter afferents due to the demyelinating lesion at the cervical level.
Adult↗
Conduction abnormalities induced by sera of patients with multifocal motor neuropathy and anti-GM1 antibodies.
Increased titers of anti-GM1 antibodies have been associated with motor neuron disease and motor neuropathy with or without conduction block. To investigate the pathogenetic role of anti-GM1 antibodies we injected into rat tibial nerves sera from patients with multifocal motor neuropathy and conduction block (MMN) or progressive spinal muscular atrophy (PMA), both presenting anti-GM1 antibodies. Sera of patients with MMN produced reduction of amplitude and dispersion of compound muscle action potential from proximal stimulation. Morphometry revealed demyelination in 6.2% of fibers. Sera of patients with PMA did not produce clear-cut electrophysiological or morphological changes. Differential effects of sera from patients presenting high-titer anti-GM1 antibodies, but with distinct clinical syndromes, might depend on differences in anti-GM1 antibody affinity, valency, or ability to fix complement. Alternatively, circulating factors other than, or in addition to, anti-GM1 antibodies present in sera of patients with MMN, but not of PMA patients, might be responsible for conduction abnormalities and reproduce them after passive transfer.
Animals↗
Basal ganglia involvement in multiple sclerosis with alternating side paroxysmal dystonia.
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Basal Ganglia Diseases↗
Idiopathic recurring stupor: a case with possible involvement of the gamma-aminobutyric acid (GABA)ergic system.
A patient had recurrent spontaneous episodes of stupor or coma in the absence of toxic, metabolic, or structural brain damage. Ictal electroencephalography showed fast 14 Hz background activity; sleep studies excluded narcolepsy. Flumazenil (Anexate), a benzodiazepine antagonist, promptly resolved the episodes and normalized the electroencephalogram. Radioreceptor binding studies showed the presence of a ligand to the central benzodiazepine receptor in plasma and cerebrospinal fluid during the episodes, suggesting a gamma-aminobutyric acid (GABA)ergic system involvement in the origin of the attacks.
Benzodiazepines↗
Patterns of reactivity of human anti-GM1 antibodies with spinal cord and motor neurons.
Human anti-GM1 antibodies from patients with lower motor neuron disease or predominantly motor neuropathy recognize carbohydrate determinants shared by GM1 and related glycolipids and glycoproteins, but the identity of the antigens to which they bind in tissue is unknown. We examined the binding of anti-GM1 antibodies with differing fine specificities to spinal cord, isolated motor neurons, and dorsal root ganglia neurons in order to characterize the tissue antigens. All anti-GM1 antibodies tested bound to the surface of bovine spinal motor neurons and immunostained the gray matter of unfixed sections of spinal cord. The staining was blocked by cholera toxin, which is specific for GM1, indicating that GM1 itself was the target antigen. Binding to white matter was more variable and depended on fixation and the fine specificities of the antibodies. The anti-GM1 antibodies did not bind to dorsal root ganglia neurons in tissue sections or in culture. These studies suggest that the autoantibodies might exert their effect, in part, by binding to GM1 on the surface of motor neurons, and that the absence of binding to dorsal root ganglia neurons might explain the lack of sensory abnormalities in affected patients.
Animals↗
Isolated failure of noradrenergic transmission in a case with orthostatic hypotension and hyperactivity of gastro-colic reflex.
We describe a 37-year-old man with a long-standing history of impotence and urgency of defaecation. The latter invariably followed the ingestion of food. Studies of cardiovascular autonomic function disclosed asymptomatic orthostatic hypotension due to isolated sympathetic noradrenergic failure with intact cardiac vagal control. There were no other neurological abnormalities. Levels of plasma noradrenaline and urinary vanillylmandelic acid were very low but plasma dopamine and urinary homovanillic acid were normal. A low level of dopamine-beta-hydroxylase activity was detected in plasma. The patient's parents were first cousins. The parents, the brother and the sister were investigated and clinical and biochemical studies showed no abnormalities. We conclude that this is a further observation of orthostatic hypotension due to isolated adrenergic failure with clinical and biochemical features different from cases previously described.
Adult↗
Autonomic nervous system function in myotonic dystrophy.
Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.
Adolescent↗
Anti-sulfatide antibodies in neurological disease: binding to rat dorsal root ganglia neurons.
Increased titers of anti-sulfatide antibodies were detected by ELISA in 5 of 200 patients and control subjects. All 5 patients had sensory impairment; 4 had neuropathy, and one had multiple sclerosis. Of the patients with neuropathy, 2 had a clinical syndrome of small fiber sensory neuropathy with normal electrophysiological or nerve biopsy studies, 1 had a sensorimotor axonal neuropathy associated with IgM monoclonal gammopathy, and 1 had sensorimotor neuropathy with multifocal motor conduction block and anti-GM1 antibodies. The anti-sulfatide antibodies bound to the surface of unfixed rat dorsal root ganglia neurons and human neuroblastoma cells, and to fixed sections of central and peripheral myelin. No binding was detected following intraneural injection into rat sciatic nerves. Pre-absorption with sulfatide but not with galactocerebroside eliminated the tissue binding activity. These findings indicate that increased titers of anti-sulfatide antibodies are found in patients with sensory impairment but are not restricted to a particular neurological syndrome or type of neuropathy. The significance of anti-sulfatide antibodies is uncertain although sulfatide on dorsal root ganglia neurons may be a target antigen.
Aged↗
Sympathetic skin response in hemispheric lesions.
We recorded the sympathetic skin response (SSR) from electrical nerve stimulation in 16 patients with cerebrovascular accident (CVA). Location and nature of the lesion were documented by computerized tomography (CT). Median (pre-rolandic and parietal) somatosensory evoked potentials (SEP) were also recorded. SSR was absent bilaterally in eight hemiplegics after stimulation of the plegic side and present bilaterally after stimulation of the normal side in the first weeks after CVA. Parietal and pre-rolandic SEPs were absent in the affected hemispheres. SSR was present bilaterally after stimulation of each side in the remaining CVA cases with reduced amplitude SEPs. Absence of the electrically evoked SSR in hemispheric lesions may be due to involvement of central afferent pathways or temporary suppression of suprasegmental excitatory influences.
Aged↗
Isolated bovine spinal motoneurons have specific ganglioside antigens recognized by sera from patients with motor neuron disease and motor neuropathy.
The gangliosides GM1 and GD1b have recently been reported to be potential target antigens in human motor neuron disease (MND) or motor neuropathy. The mechanism for selective motoneuron and motor nerve impairment by the antibodies directed against these gangliosides, however, is not fully understood. We recently investigated the ganglioside composition of isolated bovine spinal motoneurons and found that the ganglioside pattern of the isolated motoneurons was extremely complex. GM1, GD1a, GD1b, and GT1b, which are major ganglioside components of CNS tissues, were only minor species in motoneurons. Among the various ganglioside species in motoneurons, several were immunoreactive to sera from patients with MND and motor neuropathy. One of these gangliosides was purified from bovine spinal cord and characterized as N-glycolylneuraminic acid-containing GM1 [GM1(NeuGc)] by compositional analysis, fast atom bombardment mass spectra, and the use of specific antibodies. Among seven sera with anti-GM1 antibody activities, five sera reacted with GM1(NeuGc) and two did not. Two other gangliosides, which were recognized by another patient's serum, appeared to be specific for motoneurons. We conclude that motoneurons contained, in addition to the known ganglioside antigens GM1 and GD1b, other specific ganglioside antigens that could be recognized by sera from patients with MND and motor neuropathy.
Animals↗
Amplifications of multiple regions of the HTLV-I genome from DNA of an Italian spastic paraparesis patient but not from DNA of multiple sclerosis patients.
We searched for evidence of infection by the human T-cell lymphoma/leukemia virus type I (HTLV-I) in patients with multiple sclerosis (40 cases); brainstem encephalitis (1 case); Friedreich's ataxia (1 case); spastic paraparesis of unknown etiology (1 case). All patients were from the region of Abruzzo, Italy. Sera were all negative for anti-HTLV-I reactivity by the Western blotting (WB) analysis. DNAs from peripheral blood mononuclear cells were amplified using the polymerase chain reaction (PCR) technique with primers specific for the HTLV-I gag, pol, and env proviral regions. HTLV-I sequences were amplified only in the patient with spastic paraparesis of unknown etiology. In this case, HTLV-I infection might have been related to blood transfusions received 2 years prior to the onset of the neurologic symptoms. Members of the patient's family were negative for HTLV-I by PCR and WB. These data indicate that HTLV-I associated myelopathy is present also in Italy, but fail to substantiate an association of HTLV-I with multiple sclerosis.
Adolescent↗
Identification of glycoconjugates which are targets for anti-Gal(beta 1-3)GalNAc autoantibodies in spinal motor neurons.
Human IgM anti-Gal(beta 1-3)GalNAc antibodies which bind to GM1 and GD1b, are implicated in the pathogenesis of predominantly motor neuropathy or motor neuron disease. By immunofluorescence microscopy, the human antibodies immunostain the surface of motor neurons from bovine spinal cord. The motor neurons are also immunostained by cholera toxin (CT), which is specific for GM1. Glycolipid analysis using thin-layer chromatography (TLC) and immunostaining reveals that the relative concentration of GM1 and GD1b in motor neurons is greatly reduced in comparison to whole spinal cord, and that other motor neuron gangliosides are unreactive with the anti-Gal(beta 1-3)GalNAc antibodies. By Western blot analysis, the antibodies react with several protein bands in motor neuron extracts, and many of the same proteins are also recognized by PNA. These data suggest that both glycoproteins and glycolipids might be targets for anti-Gal(beta 1-3)GalNAc antibodies in spinal motor neurons.
Animals↗
HTLV-1-associated myeloneuropathy in an Italian.
A 58-year old man presented with slowly progressive spastic paraparesis, ataxia, absent ankle jerks, bladder disturbances, impairment of vibration sense and mental deterioration. Electrophysiological studies documented axonal sensory neuropathy, posterior column and optic nerve involvement. Serum tests for anti-HTLV-1 antibodies were negative but HTLV-1 proviral sequences were consistently demonstrated in white blood cell genomic DNA using the polymerase chain reaction technique. Western blot and polymerase chain reaction assays of sera and DNA from family members were negative for HTLV-1. The most likely cause of infection in this patient was a blood transfusion received 2 years before onset of symptoms. This is the second Italian case of HTLV-1 associated myelopathy and the fourth reported in white subjects living in Europe.
Amino Acid Sequence↗