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Biomedical subjects

N Canal

Publications and source records attributed to N Canal.

At least 55 records · Page 3Linked to original sources

Influence of clinical variables on neuropsychological performance in multiple sclerosis.

The effects of age, educational level, duration and course of the disease, physical disability and mood status on several cognitive functions (short- and long-term memory, frontal functions, attention, language and visuospatial skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton Depression Rating Scale (HDRS) scores and a secondary progressive disease course significantly influenced neuropsychological performance. Factorial analysis revealed that indexes of (1) frontal function impairment, (2) long-term verbal memory and language function impairment, and (3) visuospatial short- and long-term memory and visuoperceptive function impairment accounted for 85% of the variance in neuropsychological performance. Only the first factor was significantly related to the presence of depressive symptomatology, as assessed by the HDRS. These results indicate that both the course of the disease and the presence of affective disorders must be taken into account when evaluating the natural history of cognitive impairment in MS and suggest that depressive symptomatology and cognitive dysfunction in MS are related to the involvement of at least partially overlapping anatomofunctional circuits.

Adult↗

Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent.

In developing and regenerating peripheral nerve, Schwann cells interact with axons and extracellular matrix in order to ensheath and myelinate axons. Both of these interactions are likely to be mediated by adhesion molecules, including integrins, which mediate cell-cell and cell-extracellular matrix interactions. Recently, the beta 4 integrin subunit was reported to be expressed by Schwann cells in peripheral nerve. We have examined the expression of beta 4, beta 1 and their common heterodimeric partner, the alpha 6 integrin subunit, in developing and regenerating rat peripheral nerve. beta 4 and alpha 6 are enriched in peripheral nerve and they co-localize at the abaxonal surface of myelinating Schwann cells, opposite the Schwann cell basal lamina, which contains possible ligands of alpha 6 beta 4. In contrast, beta 4 and alpha 6 are expressed in a different pattern in non-myelinating Schwann cells. The level of beta 4, but not alpha 6 or beta 1 mRNAs, increases progressively in developing nerves, reaching a peak in adult nerves well after the peak of the myelin-specific mRNAs. After axotomy, the expression of beta 4 mRNA and protein, but not alpha 6 or beta 1 mRNAs, fall rapidly but subsequently are reinduced by regenerating axons. Similarly, in cultured Schwann cells, the expression of beta 4 mRNA, but not alpha 6 mRNA, is significantly modulated by forskolin, a drug that elevates cAMP and mimics some of the effects of axonal contact. beta 4 integrin expression in Schwann cells, therefore, is regulated by Schwann cell-axon interactions, which are known to be critical in determining the Schwann cell phenotype. Furthermore, the polarized expression of alpha 6 beta 4 to the abaxonal surface of myelinating Schwann cells suggests that alpha 6 beta 4 may mediate in part the morphological changes required of Schwann cells in the process of myelination in the peripheral nervous system.

Amino Acid Sequence↗

A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy.

OBJECTIVE: Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease patient morbidity by allowing for potential therapeutic interventions. We have designed an outpatient program to facilitate diagnosis of diabetic neuropathy. RESEARCH DESIGN AND METHODS: Patients are initially administered a brief questionnaire and screening examination, designated the Michigan Neuropathy Screening Instrument (MNSI). Diabetic neuropathy is confirmed in patients with a positive assessment by a quantitative neurological examination coupled with nerve conduction studies, designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56 outpatients with confirmed type I or II diabetes were administered the standardized quantitative components required to diagnose and stage diabetic neuropathy according to the San Antonio Consensus Statement (1) and the Mayo Clinic protocol (2). These same patients were then assessed with the MNSI and the MDNS. RESULTS: Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy. Twenty-eight patients with an MDNS of > or = 7 had neuropathy, while 21 non-neuropathic patients had a score < or = 6. Of 35 patients with diabetic neuropathy, 34 had > or = 2 abnormal nerve conductions. Twenty-one normal patients and one patient with neuropathy had < or = 1 abnormal nerve conduction. CONCLUSIONS: The results indicate that the MNSI is a good screening tool for diabetic neuropathy and that the MDNS coupled with nerve conductions provides a simple means to confirm this diagnosis.

Adult↗

Serum antibodies to Purkinje cells and dorsal root ganglia neurons in sensory neuronopathy without malignancy.

Anti-Purkinje cell antibodies (APCA), believed to be markers of paraneoplastic cerebellar degeneration in females, have been identified in the serum of 3 men with subacute sensory neuronopathies and no evidence of tumors 5 years after the onset of the neurological signs. By indirect immunohistochemistry on sections of rat cerebellum and dorsal root ganglia, the patients' IgG bound to the cytoplasms of both Purkinje cells and dorsal root ganglia neurons. By western blot analysis on whole human cerebellum and whole human dorsal root ganglia homogenates, the IgG from 2 patients bound to a 62-kd protein in both homogenates and the IgG from 1 patient bound to a 110-kd protein in the cerebellum homogenate only. Yo autoantibody test was negative in all patients. Our study provides evidence that non-anti-Yo APCA may be associated with subacute sensory neuronopathies and are not necessarily markers of an underlying tumor. The previously described anti-Yo APCA has only occurred in females with cancer.

Aged↗

Neurophysiological evaluation in detrusor instability.

Different and complex neuronal systems are involved in the control of continence. Detrusor overactivity has been divided by the International Continence Society into two functional subgroups: a) detrusor instability and b) detrusor hypereflexia. Only in the latter group has neurological damage been shown, but pathophysiological mechanisms are still unknown. In order to complete a full investigation of sensory and motor pathways 12 female patients affected by idiopathic detrusor instability (mean age 60.2 years; range 49-73) and 13 age-matched healthy women were studied. All patients were submitted to a subtracted cistometrogram (CMG), anal sphincter electromyography (EMG) with a bipolar coaxial needle, sacral reflex analysis after stimulation of the dorsal nerve of the clitoris, tibial and pudendal somatosensory evoked potentials, motor evoked potentials after magnetic cortical coil stimulation, and recording from anal sphincter and abductor brevis hallucis muscles. All patients had normal neurophysiological tests, and no significant differences between patients and controls could be seen. Our data confirms the absence of both clinical and subclinical damage of central sensory or motor pathways in detrusor instability; an alteration of suprasegmental mechanisms cannot be excluded.

Adult↗

Acute presentation of Tangier polyneuropathy: a clinical and morphological study.

We describe a patient with Tangier disease and a peripheral neuropathy with an unusual acute onset. The morphological studies of sural nerve biopsy revealed both axonal degeneration and demyelination, and the fiber loss was preferentially restricted to two of ten nerve fascicles. The cytoplasm of Schwann cells, fibroblasts, macrophages and pericytes were vacuolated because of the presence of numerous lipid droplets. The clinical and morphological findings are consistent with the possibility that ischemia plays a major role in causing this neuropathy.

Female↗

Bilateral eighth cranial nerve neuropathy in human immunodeficiency virus infection.

A 21-year-old HIV-1 seropositive African man developed an acute febrile illness followed by a sudden sensorineural bilateral hearing loss. Neurophysiological studies demonstrated the bilateral involvement of both branches of the vestibulocochlear cranial nerves. Immunological studies revealed the presence of an ongoing central nervous system HIV-1 infection. A sural nerve biopsy showed the presence of inflammatory cells. We suggest HIV testing for all cases of sudden onset of bilateral hypoacusia.

Acquired Immunodeficiency Syndrome↗

Effects of acute doses of oxiracetam in the scopolamine model of human amnesia.

The scopolamine model of amnesia has been used to test the pharmacodynamic efficacy of oxiracetam in 12 healthy volunteers. The subjects were divided into four experimental groups, according to a double-blind cross over incomplete randomized block design. After a baseline neuropsychological examination, each subject received in two separate sessions one of the following treatments, as acute oral doses: oxiracetam 800, 1600, 2400 mg or placebo. One hour after treatment scopolamine hydrobromide (0.5 mg) was given subcutaneously. The cognitive performance was tested before and 1, 2, 3 and 25 h after scopolamine administration. Scopolamine caused a deterioration of performance of verbal episodic memory, semantic memory and attention tests. In comparison to placebo, oxiracetam improved the overall test performance, with a statistically significant difference at the dose of 1600 mg on delayed recall of word lists, and showed dose-related antagonism of scopolamine-induced effects also on semantic memory and attention. The efficacy of an acute dose of oxiracetam in reducing scopolamine-induced cognitive impairment supports the potential usefulness of this pharmacological model of amnesia for studying the effects of cognition enhancers in humans.

Adult↗

Brain magnetic resonance imaging correlates of cognitive impairment in multiple sclerosis.

We evaluated the correlations between cognitive impairment, clinical and brain magnetic resonance imaging (MRI) findings in 100 patients with multiple sclerosis (MS). The performance on one or more neuropsychological tests was abnormal in 47% of the 64 patients who completed the entire neuropsychological battery; the cognitive impairment was mild in 14 (22%) and severe in 16 (25%). Performance on any single neuropsychological test was unrelated to clinical parameters (age, duration of the disease, disability). The neuropsychological performance of relapsing-remitting patients was better than in patients with a chronic-progressive disease. The mean scores for almost all the neuropsychological tests were significantly lower in patients with severe ventricular dilatation and corpus callosum atrophy than in patients in whom these structures were little affected. Mean scores for WMS, performance Intelligence Quotient (IQ), total IQ and Token Test (TT) were also significantly correlated with the widening of cortical sulci and total lesional scores. Our data support the contention that the involvement of pathways that are critical for a given cognitive process as well as the progression of the axonal degeneration and sclerosis seem to play important roles in the pathophysiology of cognitive dysfunction in MS.

Adult↗

Antibodies to sulfatide and to chondroitin sulfate C in patients with chronic sensory neuropathy.

Sera from eight of 25 patients with chronic sensory neuropathy had high titers of antibodies to sulfatide and chondroitin sulfate C or both. Preclearing of patients' sera with either sulfatide or chondroitin sulfate C revealed that in four patients the antisulfatide antibodies crossreacted with chondroitin sulfate C. By indirect immunohistochemistry sera reactive to sulfatide only had a different staining pattern from those reactive to both sulfatide and chondroitin sulfate C. By direct immunohistochemistry we found immunoglobulins bound to nerve fibers only in patients with serum antibodies against both sulfatide and chondroitin sulfate C. Our study provides evidence that antibodies to sulfatide and to chondroitin sulfate C differ in their fine specificity and are present in 30% of patients with chronic sensory neuropathy.

Adult↗

Effect of hypothyroidism on rat peripheral nervous system.

The function and structure of the peripheral nervous system of Sprague-Dawley rats, 3 months after the induction of hypothyroidism by administration of N-propylthiouracil in drinking water, has been studied. The motor action potential amplitude of the caudal nerve showed a significant reduction (p < 0.001) when compared with an age-matched control group of animals. Computer-assisted morphometric analysis of sciatic nerves of hypothyroid rats showed normal distribution and density of myelinated fibers, and a normal axon/myelin ratio. Electron microscopy revealed only minor alterations in axons of myelinated fibers characterized by a dissolution of neurotubules. After two months of substitution therapy these effects were reversed. The present data suggest that early impairment of nerves induced by hypothyroidism is rare and could be related to metabolic alterations rather than to structural changes and is reversible with hormone treatment.

Action Potentials↗

SPET imaging of cerebral perfusion in patients with non-refractory temporal lobe epilepsy.

The pattern of regional cerebral blood flow was assessed by single photon emission tomography and (99mTc)HM-PAO in 28 patients with clinical diagnosis of non-refractory cryptogenic temporal lobe epilepsy on chronic treatment with carbamazepine. Each patient underwent a magnetic resonance imaging study of the brain. An EEG was performed concurrently with the assessment of cerebral blood flow. Areas of focal hypoperfusion were observed in 8/28 patients, and a concurrent EEG focus was identified in 10/28 patients. Areas of hypoperfusion and the EEG foci were consistent in 6 of the 10 patients with EEG abnormalities; in 2 patients hypoperfusion and the EEG abnormalities were on opposite sides, though in homologous areas; in 2 patients the perfusion pattern was normal in spite of the EEG abnormalities. The number of clinical seizures and EEG abnormalities was higher for the patients presenting with cerebral hypoperfusion than for those with normal perfusion. It is concluded that the evaluation of cerebral blood flow may provide useful information for both diagnostic and prognostic assessment of these patients.

Adult↗

Lambert-Eaton myasthenic syndrome and polyneuropathy in a patient with epidermoid carcinoma of the lung.

We describe a patient affected by the Lambert-Eaton myasthenic syndrome, sensory motor axonal neuropathy and epidermoid carcinoma of the lung. Serum autoantibodies to voltage-operated calcium channels were detected. After lobectomy, voltage-operated calcium channel-related structures were demonstrated in the patient's tumor. By immunocytochemistry, the patient's IgG reacted with neural structures and particularly with intermediate filaments. We think that these autoantibodies may be implicated in the pathogenesis of the neurological symptomatology.

Aged↗

Brain stem magnetic resonance imaging and evoked potential studies of symptomatic multiple sclerosis patients.

In this study we evaluated the sensitivity of neuroradiological and neurophysiological tests for detecting brain stem (BS) lesions in multiple sclerosis patients, since the recent introduction of the gradient motion rephasing technique has markedly increased the image quality of magnetic resonance imaging (MRI). From 50 MS patients (33 women and 17 men; mean age 35.9 +/- 8.3 years; mean duration of the disease 7.2 +/- 4.1 years) with clinical signs of BS involvement, brain MRI, BS auditory evoked potentials (BAEPs), and left and right median somatosensory evoked potentials (mSEPs) were obtained. BS MRI lesions were detected in 41 patients (82%); in 14 cases they were located in the medulla oblongata, in 55 in the pons, and in 24 in the midbrain. Single lesions were present in 20 patients, while two or more BS lesions were demonstrated in 21 patients; 30 patients had at least one lesion located close to the inner or the outer cerebrospinal fluid border. BAEPs were abnormal in 19 of the 50 patients (38%), and BS components of mSEPs were abnormal in 15 of 46 (33%). With combined use of these neurophysiological techniques, BS abnormalities were revealed in 24 patients (48%). Only 1 patient had neurophysiological BS abnormalities and normal MRI. Moreover, there was a good correlation (74%) between the clinical and MRI BS findings in the 23 patients with signs referable to focal neurological BS lesions. The concordances considering clinical and evoked potential reports were positive, but less marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice.

We have studied the effects of chronic treatment with recombinant interleukin-2 on the central nervous system of adult and old mice. Treatment with high doses of recombinant interleukin-2, on a schedule similar to that used in humans, was started at the age of 4 and 17 months, respectively, and ended 3 months later. At that time, all the mice were tested for acquisition of a passive-avoidance task and then sacrificed for histological examination. Three of the four groups (treated and control adults and control old mice) did not differ from one another in task performance or neuron density in frontal cortex, cerebellum, dentate gyrus or CA1-2, CA3, CA4 hippocampal areas. The old treated mice were unique in showing impairment of the mnesic functions and marked neuronal cell loss and degenerative changes limited to the hippocampal regions. Immunohistochemical studies did not show any significant amount of immunoglobulins in affected areas. Our results suggest that in old mice the impairment of the mnesic functions after recombinant interleukin-2 administration is due to hippocampal neuronal damage.

Aging↗

Effects of hyperglycaemia on visual evoked potentials in insulin-dependent diabetic patients.

Multimodality evoked potentials frequently reveal subclinical involvement of the central nervous system in patients with insulin-dependent diabetes mellitus. We devised this study to evaluate the possible effects of acute hyperglycaemia on visual evoked potential (VEP) parameters in type 1 diabetic patients. A hyperglycaemic clamp (250 mg/dl for 180 min) was performed in ten patients. Monocular pattern reversal VEPs (check size 15', contrast 50%) were recorded before, and every 30 min after the start of the clamp. Basal VEP latencies and amplitudes were normal bilaterally in nine patients. No significant changes in pattern reversal and flash VEP parameters were observed after the induction or during the clamp period. None of the neurophysiological parameters evaluated during the test was related to the duration of the disease, the basal VEP latency or amplitude or the presence of retinopathy. Our data suggest that the neurophysiological abnormalities detected in insulin-dependent diabetic patients are due to structural involvement of the central nervous pathways and not to functional damage induced by acute short-term hyperglycaemia.

Adult↗

Relationship between corpus callosum atrophy and cerebral metabolic asymmetries in multiple sclerosis.

Corpus callosum (CC) atrophy by magnetic resonance imaging (MRI) is a common finding in multiple sclerosis (MS). In order to examine the relationship between CC atrophy and cortical brain metabolism, we compared the cerebral metabolic rates for glucose (CMRglc), measured by positron emission tomography (PET), of 8 MS patients with evidence of CC atrophy on midsagittal MRI, 8 MS patients without CC atrophy and 10 healthy controls. Results showed no significant differences in supratentorial CMRglc absolute values between the three groups, although a slight metabolic reduction was observed in both MS groups compared with normal controls. By contrast, only patients with CC atrophy showed greater directional metabolic asymmetry than normals, the left frontal, temporal and parietal association cortices being significantly lower than the right. Predominant left hemispheric metabolic reductions were not accompanied by a corresponding left-sided predominance in the extent of MRI-detected demyelinating lesions. Therefore our data suggest that CC atrophy interfers more with left than with right metabolic function.

Adult↗

IgG monoclonal proteins from patients with axonal peripheral neuropathies bind to different epitopes of the 68 kDa neurofilament protein.

We describe three patients with a sensorimotor axonal polyneuropathy and an IgG M-protein that binds to a 68 kDa axonal protein identified as the low molecular weight neurofilament protein (NF-L). The immunological studies revealed that the M-proteins have different target epitopes: one is phosphorylated and the other two are nonphosphorylated. One of the nonphosphorylated epitopes is common to other intermediate filaments, such as desmin and vimentin.

Axons↗