Aspects of peripheral nerve involvement in patients with treated hypothyroidism.

BACKGROUND: We studied involvement of large and small nerve fibres in patients with hypothyroidism and symptoms and signs of polyneuropathy. METHODS: Sixteen patients with established diagnosis of hypothyroidism were extracted from a patient population participating in a 'polyneuropathy study'. In addition, seven patients with other additional potential causes of polyneuropathy than hypothyroidism were investigated. The patients underwent neurological examination, routine blood tests, nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsies with assessment of intraepidermal nerve fibre (IENF) density. RESULTS: Sixty-three per cent of the patients with 'pure' hypothyroidism had abnormalities on NCS, 25% had reduced IENF density and 31% had abnormalities on QST. Four patients (25%) met criteria for small fibre polyneuropathy, the other (75%) were classified as having mixed fibre polyneuropathy. There were no differences in the amount of abnormalities on NCS, QST and skin biopsy between patients with hypothyroidism and those with hypothyroidism and other potential causes of polyneuropathy. CONCLUSIONS: The majority of patients with hypothyroidism had involvement of both large and small nerve fibres. However, some patients had isolated small fibre polyneuropathy. Patients with 'pure' hypothyroidism had essentially the same degree of peripheral nerve fibre involvement as those with other additional causes of polyneuropathy.

Quantitative sensory testing in patients with polyneuropathy and healthy individuals.

AIMS: Elderly individuals and patients with polyneuropathy often feel heat pain or burning sensation on quantitative sensory testing (QST) of warm perception distally in the lower limbs. We therefore studied heat pain threshold (HPT), warm perception threshold (WPT) and the difference between heat pain and warm perception thresholds in 48 patients with symptoms and signs of polyneuropathy matched according to age and gender with 48 healthy persons. METHODS: QST (using method of limits) was performed on the distal calf and the dorsal foot. RESULTS: Particularly in the neuropathy group several individuals (58%) had an unpleasant feeling, often burning, when the thresholds according to the WPT algorithm were recorded. Difference between heat pain and warm perception thresholds in the lower calf of the patients was 3.9 +/- 3.5 and 5.8 +/- 3.4 degrees C in the controls (P = 0.012), and on the foot 3.8 +/- 2.8 vs 5.3 +/- 3.6 degrees C (P = 0.02). CONCLUSIONS: When performing QST it is important to assess also quality features of warm perception, such as burning and heat pain sensation.

Idiopathic polyneuropathy and impaired glucose metabolism in a Norwegian patient series.

BACKGROUND AND PURPOSE: North American studies have indicated a high prevalence of impaired glucose tolerance (IGT) in patients with sensory polyneuropathy. We searched for the occurrence of IGT in a Norwegian patient material with polyneuropathy. METHODS: Seventy patients with symptoms and signs of sensory polyneuropathy were included. Cases with known causes of neuropathy were excluded. All patients underwent a 2 h oral glucose tolerance test (OGTT). Nerve conduction studies (NCS), quantitative sensory testing (QST) and skin biopsy with assessment of intra-epidermal nerve fibre (IENF) density were performed. RESULTS: Sixteen patients (23%) had impaired glucose metabolism (IGM): 2 (3%) were found to have diabetes, 9 (13%) had IGT, 3 (4%) had impaired fasting glucose (IFG) and 2 (3%) both IFG and IGT. About 62% of the patients with IGM and polyneuropathy and 50% of those with chronic idiopathic axonal polyneuropathy (CIAP) had abnormalities on NCS. Reduction of IENF occurred in 37% of the patients with IGM and 43% of those with CIAP. CONCLUSIONS: Patients with polyneuropathy and IGM had essentially the same degree of involvement of small and large nerve fibres as patients with CIAP. IGT seems less frequent in Norwegian patients with polyneuropathy than reported in North American populations.

A rare form of painful nondystrophic myotonia.

OBJECTIVE: In this paper we report a painful nondystrophic myotonia which has not been previously described. Pain is a rare symptom in myotonia. We report a myotonic disorder in a 34-year-old woman and her 14-year-old daughter. Painful cramps occur during and after exercise in the mother, and both patients can demonstrate unusual contractions in the tongue. In the present study we try to evaluate the mechanisms behind the unique finding of trains of high amplitude of positive waves, not seen in the earlier known myotonic conditions. METHODS: Clinical investigations and electromyography with single and dual channel recordings and muscle morphometry were performed. RESULTS: The electromyographic recordings reveal positive waves, fibrillation potentials and myotonic discharges. In addition, extraordinary findings were made of trains of high frequency positive potentials with very high amplitudes and with conduction block along the muscle fibres. CONCLUSIONS: In this new form of myotonia with likely dominant heredity, the specific finding of trains of high amplitude positive waves indicates ephaptic transmission within bundles of neighbouring muscle fibres.

Organic brain disease in psychogeriatric patients: impact of symptoms and screening methods on the diagnostic process.

Psychogeriatric patients are mentally affected by a heterogeneous group of diseases, traditionally classified as functional or organic brain disorders (OBDs). Here, we evaluate screening procedures with respect to revelation of underlying OBD. Fifty consecutive patients admitted to a psychogeriatric unit dedicated to late-onset psychiatric disease were included. Diagnosis at admission, symptoms, and time of onset of disease were determined blindly by an independent, experienced psychiatrist on the basis of referral documents and the interview written at admission. Subsequently, consensus established a clinical diagnosis (after psychiatric and neurologic evaluations) and a final diagnosis after the screening procedures (Cognistat and MMS-tests, electroencephalograms, computed tomography, and SPECT). Conventional criteria (ICD-10, ICPC) were used for diagnostic classification. Only 10 of the 50 patients were diagnosed with OBD at admission and an additional 7 patients following full clinical evaluations. At final diagnosis, 34 (of 46) patients were diagnosed with significant OBD. The Cognistat test had the largest diagnostic impact, with sensitivity/specificity values of 81%/60% for OBD.

Peripheral neuropathy caused by severe hypothermia.

OBJECTIVE: To report follow-up data in the evaluation of peripheral neuropathy in a 29-year old female after accidental deep hypothermia (13.7°C) in 1999. METHODS: Nerve conduction studies (NCS) and electromyography (EMG) were performed 20 days after the accident and again after 5 months and 1, 3, 5 and 11 years. Macro EMG was performed after 3, 5 and 11 years. To evaluate small fiber function, RR-interval, sympathetic skin response, quantitative sensory testing and skin biopsy for quantification of intra-epidermal nerve fiber density were performed in 2009. RESULTS: In the intensive care unit sensory and motor responses were absent except for the tibial nerves, and EMG showed profuse denervation. Improvement of amplitudes and conduction velocities was seen during the first 5 years. Muscular atrophy of hand muscles persisted. Large fibers were involved more extensively than small fibers. CONCLUSIONS: A severe axonal sensorimotor polyneuropathy developed in the intensive care unit following severe hypothermia. The mechanism was most likely cold injury to peripheral nerves. SIGNIFICANCE: The clinical picture and the laboratory findings indicate that even multi-organ dysfunction and, of specific interest in this study, a severe axonal degeneration may come to a good restitution after long time.

Intraepidermal nerve fibre density, quantitative sensory testing and nerve conduction studies in a patient material with symptoms and signs of sensory polyneuropathy.

Small diameter nerve fibre (SDNF) neuropathy is an axonal sensory neuropathy affecting unmyelinated (C) and thin myelinated (A-delta) fibres. We have evaluated 75 patients with symptoms and signs suggesting SDNF dysfunction with or without symptoms and signs of co-existing large diameter nerve fibre involvement. The patients were examined clinically and underwent skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS). The purpose of this study was to compare the relationship between the different methods and in particular measurements of thermal thresholds and intraepidermal nerve fibre (IENF) density in the same site of the distal leg. The main subdivision of the patient material was made according to the overall NCS pattern. Patients with normal NCS (38) had 6.4 +/- 3.8 and patients with abnormal NCS (37) had 4.4 +/- 3.4 IENF per mm (P = 0.02). Limen (difference between warm and cold perception thresholds) was significantly higher (more abnormal) in those with abnormal than in those with normal NCS (22.1 +/- 9.1 vs. 13.4 +/- 5.6, P < 0.0001). Cold perception threshold was more abnormal (P < 0.0001) than warm perception threshold (P = 0.002). Correlation between IENF and QST was statistically significant only when NCS was abnormal, and thus dependent of a more severe neuropathic process in SDNFs.

[Small fiber neuropathy]. / Tynnfiberneuropati.

A common sign of distal small fibre neuropathy is dysesthesias, especially burning sensation distally in the extremities. These symptoms are often difficult to treat with conventional analgesics. In the course of the disease, the patient may become less sensitive to pain and changes in temperature, but clinical signs may nevertheless be minor and often difficult to detect by clinical examination. Dysautonomic features are also common. Selective affection of small fibres may occur in the form of pure small fibre neuropathy, but this may also be an early manifestation of general sensorimotor polyneuropathy. Common causes are diabetes mellitus, alcoholism, and amyloidosis. Abnormalities in small diameter fibres may be detected by quantitative sensory testing of temperature and pain thresholds, and by autonomic tests. We describe four patients with polyneuropathy with a predominance of small fibre involvement.

Human leukocyte antigen class I in polymyositis: leukocyte infiltrates, regeneration, and impulse block.

In polymyositis (PM), T-cell mediated myocytotoxicity is directed against strongly human leukocyte antigen class I positive (HLA-I+) muscle fibers. Fiber regeneration probably is partly responsible for this HLA-I up-regulation. We have evaluated regeneration, denervation/impulse blockade, and focal leukocyte infiltrates as possible HLA-I inducing factors in PM. Distinctive patterns of HLA-I, nerve cell adhesion molecule (NCAM), and vimentin expression accompany denervation and regeneration. Regenerating fibers also have centralized nuclei. Using semiquantitative methods, we examined strongly HLA-I+ fibers in PM muscle biopsies for these markers. Sarcoplasmic HLA-I levels were related to the presence of leukocyte infiltrates and invasion of fibers. Strongly HLA-I+ fibers were frequently invaded, and regeneration-associated changes were usually observed at sites of fiber damage. Sarcoplasmic HLA-I levels were stable along intact fibers, also adjacent to leukocyte infiltrates. A majority of the strongly HLA-I+ fibers were nonregenerating (NCAM+ only). Though other mechanisms cannot be excluded, this suggests that impulse blockade or denervation may contribute to extra HLA-I up-regulation in these fibers.

Peripheral neuropathy in systemic lupus erythematosus--a longitudinal study.

OBJECTIVE: Peripheral neuropathy (PN) is reported to occur in 5-27% of patients with systemic lupus erythematosus (SLE) mostly as a length-dependent sensorimotor axonopathy. Studies over time have not been performed. Design - Longitudinal study. SUBJECTS AND METHODS: Thirty-three Caucasian SLE patients consented to participate in the study and were subjected to clinical examination, laboratory tests, and nerve conduction velocity (NCV) studies. At the follow-up 7 years later, 7 patients (21%) were dead, 4 refused to participate, and 2 did not want to perform NCV studies. Twenty patients were thus available for longitudinal study. RESULTS: When all SLE patients were considered on a group basis at follow-up, 8 (33%) out of 24 NCV parameters showed significant deterioration despite correction for time, while 16 (67%) were unchanged. Analysis of change from baseline showed that, except for F-responses, several NCV changes were highly dependent (negative regression coefficients) on baseline levels at start of study. No demographic, laboratory, or disease associated quantitative factor was associated with these changes in NCV parameters over time. Nor was a consistent effect on NCV parameters from any qualitative demographic or disease associated factor confirmed by Repeated Measures ANOVA analyses. CONCLUSIONS: A modest progressive neuropathic process exists in patients with SLE. Important is also the finding that, over time, the abnormalities of NCV parameters fluctuate in the individual patients, and the impairments are not necessarily irreversible. This study also shows no association to medication, demographic-, or other disease associated factors.

Noncleavable transmembrane mouse tumor necrosis factor-alpha (TNFalpha) mediates effects distinct from those of wild-type TNFalpha in vitro and in vivo.

Tumor necrosis factor-alpha (TNFalpha) exists in two biologically active forms, a 26-kDa transmembrane form and a proteolytically cleaved and secreted form. We sequentially inactivated all three known cleavage sites of mouse TNFalpha by mutating the corresponding DNA sequences. A murine T cell hybridoma transfected with the nonsecretable mutant TNFalpha efficiently lysed L929 target cells in a cell contact-dependent manner and induced expression of vascular cell adhesion molecule-1 on mouse endothelioma cells. A genomic mouse TNFalpha clone encoding this mutant was subsequently introduced as a transgene into TNFalpha(-/-) lymphotoxin-alpha(-/-) mice. The 3' AU-rich regulatory elements of the TNF locus were maintained in the transgene to assure adequate gene regulation. Transmembrane TNFalpha transgenic mice were fully protected from endotoxic shock, and no TNFalpha bioactivity was detectable in the serum after stimulation with lipopolysaccharide. Activated CD4 T cells from these animals, however, lysed L929 cells in a cell contact-dependent way. After administration of lipopolysaccharide, transmembrane TNFalpha transgenic mice produced significantly higher levels of interleukin-12 than wild-type mice or TNF-deficient mice. This indicates that transmembrane TNFalpha may greatly affect the course of a cellular immune responses in vivo and exerts quantitatively and qualitatively distinct functions from secreted TNFalpha in vitro and in vivo.