Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy

Small fibre neuropathy (SFN) has been demonstrated in sarcoidosis. However, a systematic analysis of neuropathic pain and autonomic symptoms, key features of SFN, has not been performed. Clinimetric evaluation of pain and autonomic symptoms using the neuropathic pain scale (NPS) and the modified Composite Autonomic Symptoms Scale (mCOMPASS) was used in sarcoidosis patients for this study. A total of 91 sarcoidosis patients (n = 23 without SFN symptoms, n = 43 with SFN symptoms but normal intraepidermal nerve fibre density (IENFD), n = 25 with SFN symptoms and reduced IENFD) were examined. NPS and mCOMPASS were assessed twice (reliability studies). Severity of pain was compared between the subgroups. Correlation between NPS and a visual analogue pain scale (VAS) was assessed (validity studies). Healthy controls (n = 105) completed the mCOMPASS for comparison with patients’ scores. Patients with sarcoidosis, SFN complaints, and reduced IENFD demonstrated more severe pain scores on the NPS. The mCOMPASS differentiated between subjects with and without SFN symptoms. A significant correlation was obtained between the NPS and VAS, indicating good construct validity. Good reliability values were obtained for all scales. The use of the NPS to evaluate SFN symptoms is suggested, as it shows differences between patients with SFN symptoms with normal or reduced IENFD values. The mCOMPASS might be used to select patients for further testing.     

The extent of small fibre sensory neuropathy in diabetics with plantar foot ulceration.

Thresholds for cutaneous warming and cooling stimuli were measured in 20 diabetics with neuropathic foot ulcers. All patients had a profound disturbance of sensory perception in the ulcerated foot with complete loss of perception of warming; thresholds for vibration and cooling were highly abnormal in all but two patients. Measurements of thermal threshold were made on both feet in 10 patients: warming was lost bilaterally in all, and cooling was bilaterally absent in six. There was no clear pattern of sensory loss in those diabetics with unilateral foot ulceration to suggest that sensory impairment was the determining factor for the development of a plantar ulcer. Measurements of thermal thresholds were made at additional sites in 13 patients and although the most marked abnormalities of sensation were always found in the feet, in some severe neuropaths, abnormal thresholds on the hand and even the face were demonstrated. Thresholds for warming were invariably more abnormal than thresholds for cooling. The diabetics with neuropathic ulceration in this study all had severe generalised peripheral nerve disease involving large myelinated as well as both small myelinated and unmyelinated sensory fibres. The quantitative evidence on the distribution of sensory loss for thermal sensations supports the hypothesis that the neuropathic process affecting the small myelinated and unmyelinated fibres is length dependent.     

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically. The facial nerve motor neurography was abnormal in 17 of 19 HMSN I patients and in both HMSN III patients, revealing moderate to marked conduction slowing in both the extracranial and intracranial nerve segments, along with variable reductions of compound muscle action potential (CMAP) amplitudes. The facial nerve conduction slowing paralleled that of limb nerves, but was not associated with clinical dysfunction of facial muscles, because none of the HMSN I patients had facial palsy. Conduction slowing was most severe in the HMSN III patients, but only slight facial weakness was present. In GBS, conduction slowing was less marked, but facial weakness exceeded that in HMSN patients in all cases. We conclude that involvement of the facial nerve is common in HMSN I and HMSN III. It affects the intra- and extracranial part of the facial nerve and is mostly subclinical.     

Blood lactate threshold and type II fibre predominance in patients with exertional heatstroke.

OBJECTIVES: Severe damage to skeletal muscle is usually seen in patients with exertional heatstroke. Thirty seven young military recruits with exertional heatstroke in Taiwan from 1992 to 1995 were studied to evaluate changes in muscle pathology and blood lactate with exercise. METHODS: A biopsy sample of the vastus lateralis was taken from recruits within 10 days of the initial presentation. Results were compared with those from 15 controls matched for age and sex. During the recovery period, 90-150 days after exertional heatstroke, 29 patients participated in a constant work load test on the treadmill to assess their blood lactate threshold, and a second biopsy sample was taken. Each biopsy was examined histologically for pathology, distribution of fibre types, and fibre diameter. RESULTS: Twenty four of the 37 patients with exertional heatstroke developed rhabdomyolysis and 18 of these had type II fibre predominance in their muscle biopsy. The patients with type II fibre predominance had a higher tendency to develop rhabdomyolysis (chi 2 = 6.84, P < 0.01). The time required to reach a blood lactate threshold during a constant treadmill work load after recovery was significantly shorter in the patients with exertional heatstroke who had type II fibre predominance (P < 0.01). There was a positive correlation between the highest value of blood lactate and the percentage of type II fibres in all tested subjects (r = 0.82, P < 0.01). CONCLUSION: Patients with type II fibre predominance are more susceptible to exertional heatstroke and tend to have a higher blood lactate concentration and a shorter time to reach blood lactate threshold under a treadmill load test.     

Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes

Observations were made on myelinated fibre regeneration in diabetic sensory polyneuropathy assessed in sural nerve biopsy specimens. These confirmed that regenerative clusters initially develop within abnormally persistent Schwann cell basal laminal tubes. The number of regenerating fibres, identified by light microscopy, was found to decline in proportion to the reduction in total myelinated fibre density. The relative number of regenerating fibres was significantly greater in patients with insulin-dependent as compared with those with non-insulin-dependent diabetes after correction for age. There was a slight negative correlation between the relative proportion of regenerating fibres and age, but this was not statistically significant. The progressive reduction in the number of regenerating fibres with declining total fibre density indicates that axonal regeneration fails with advancing neuropathy. The production of nerve growth factor (NGF) and NGF receptors by denervated Schwann cells is likely to be important for axonal regeneration. To investigate whether the failure of axonal regeneration could be related to a lack of NGF receptor production by Schwann cells, we examined the expression of p75 NGF receptors by Büngner bands immunocytochemically. In comparison with other types of peripheral neuropathy, p75 NGF receptor expression appeared to take place normally. It is concluded that failure of axonal regeneration constitutes an important component in diabetic neuropathy. Its explanation requires further investigation.These results were presented in part at a meeting of the European Association for the Study of Diabetes held in Düsseldorf in September 1994     

Neurophysiological testing correlates with clinical examination according to fibre type involvement and severity in sensory neuropathy

OBJECTIVE: To investigate a comprehensive battery of neurophysiological tests for objective evaluation of sensory neuropathies including fibre type involvement and severity, and to determine the relation between neurophysiological data and clinical examination. METHODS: 45 patients referred for sensory neuropathy were studied using a standardised clinical evaluation of large and small fibre symptoms and an original neurophysiological battery. Clinical evaluation included: assessment of tactile, vibratory, and pin sensation; tendon reflexes; toe position sense; ataxia score; pain level; and presence of trophic, vasomotor, or sudomotor abnormalities. The neurophysiological battery included: recording of large fibre and small fibre components of the sural sensory nerve action potential; somatosensory evoked cortical potentials and soleus H reflex following tibial nerve electrical stimulation; laser evoked potentials following Nd:YAG laser stimulation of the foot; and plantar sympathetic skin response to median nerve stimulation. Neuropathy was classified according to the predominantly affected fibre type, and a severity score was established based on clinical and neurophysiological abnormalities. RESULTS: On clinical examination there were 22 patients with large fibre sensory neuropathy (LFSN), 18 with mixed sensory neuropathy (MSN), and five with small fibre sensory neuropathy (SFSN). Neurophysiological classification identified 25 patients with LFSN, 13 with MSN, and seven with SFSN. Clinical and neurophysiological classifications and severity scores were correlated, whatever the type of neuropathy. CONCLUSIONS: The correlation between clinical examination and the results of an original neurophysiological test battery offers a comprehensive clinical and neurophysiological approach to the objective assessment of peripheral neuropathies according to fibre type involvement and overall severity.     

Cognitive dysfunction in patients with spinocerebellar ataxia type 6

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 6 (SCA6). We examined 13 patients with genetically confirmed SCA6 and 13 healthy control subjects matched for age, years of education, global cognitive status, and intellectual ability. We administered verbal memory (word recall and word recognition), executive function (digit span, category and letter fluency, Frontal Assessment Battery, and Trail Making Test-A and B), and visuospatial construction (figure copying) tests. We found that the patients with SCA6 had significantly lower scores on the demanding word recall and letter fluency tests compared to the control subjects, while word recognition was well preserved in the patients with SCA6. The other executive functions tested, as well as visuospatial construction, were preserved in the SCA6 group. However, although memory encoding and storage processes were preserved, the retrieval of memorized information concerning frontal function might be selectively affected in patients with SCA6 compared to in control subjects. The impaired word recall and letter fluency noted in patients with SCA6 were interpreted as being related to a word-retrieval disability. Such dysfunctions may be attributed to damage in the frontal-cerebellum circuit owing to SCA6.     

Executive dysfunction in patients with spinocerebellar ataxia type 3

The aim of this study was to assess the cognitive functions of patients with spinocerebellar ataxia type 3(SCA3). We examined 15 patients with genetically confirmed SCA3 and 15 healthy control subjects matched for age, years of education, and intellectual ability. We administered verbal memory (word recall and word recognition) and executive function tasks (word fluency test, forward and backward digit and visual span tests, Kana Pick-out Test, Trail Making Test, and conflicting instructions and a Go/NoGo task from the Frontal Assessment Battery). We found that patients with SCA3 had significantly lower scores than the healthy control subjects on the word recall, semantic, and letter fluency, and backward digit span tests, while word recognition was well preserved. The other executive function tests showed preserved functions in the SCA3 group, indicating that visual working memory, and attention and inhibition control were not affected. The patients with SCA3 showed impaired word recall and intact word recognition, and accordingly, episodic memory encoding and storage processes in short-term memory were preserved. In category and letter-fluency tests, impairment was attributable to word-retrieval from semantic memory. Impaired verbal working memory may be involved in the retrieval of verbal information from phonological storage by means of continuous subvocal rehearsal, rather than a deficit in initial phonological encoding. Essential executive dysfunction in patients with SCA3 may be due to damage in the cerebellar cortex–ventral dentate nucleus–thalamus–prefrontal cortex circuits, which are involved in strategic retrieval of verbal information from different modes of memory storage.     

Impaired finger dexterity in patients with parkinson's disease correlates with discriminative cutaneous sensory dysfunction

To study the influence of discriminative cutaneous sensory dysfunction on impaired finger dexterity in Parkinson's disease (PD), we evaluated 48 right‐handed PD patients during a practically defined off‐medication period and 24 healthy age‐matched controls. With visual deprivation, a finger tapping task (FTT) was performed to assess the speed of simple repetitive finger movements and a coin rotation task (CRT) was used to assess finger dexterity. The tasks were performed with the right hand. We measured the somesthetic temporal discrimination threshold (sTDT) in the right index finger. The mean ± SD FTT score of the patient group was lower than that of the control group (24.0 ± 8.0 vs. 29.8 ± 7.8; P < 0.01). The patient group performed worse on the CRT than the control group (8.5 ± 3.5 vs. 12.6 ± 1.7; P < 0.001). The mean sTDT value of the patient group was longer than that of the control group (124.0 ± 44.8 vs. 78.1 ± 26.2 ms; P < 0.001). The CRT scores correlated with the sTDT values (Pearson's correlation coefficient = ?0.43; P < 0.01), but not with the Unified Parkinson's Disease Rating Scale (UPDRS) finger bradykinesia scores or FTT scores. Multiple regression analysis showed that the sTDT values (parameter estimate = ?0.03, SE = 0.01; P < 0.01), but not patient age, UPDRS finger bradykinesia score, or FTT score, affected the CRT score. Slowness of simple repetitive finger movements did not have a strong impact on the impaired manual dexterity of PD. Discriminative sensory dysfunction and consequent abnormal sensorimotor integration seem to be involved in the impaired finger dexterity of PD. © 2010 Movement Disorder Society.     

Quantitative sensory testing demonstrates that subclinical sensory neuropathy is prevalent in patients with cancer

Vibration threshold (VT) determinations were used to assess the function of the large nerve-fiber sensory system in 171 patients with cancer and 58 healthy subjects. Significant differences in VT indicate dysfunction of this sensory system in the cancer group. Twelve percent of the cancer patients had elevated VT compared with 1.7% of control subjects. Elevated VT was not associated with risk factors for neuropathy such as diabetes, renal disease, poor nutrition, or treatment with chemotherapy. Although VT elevation was associated with alcoholism and increasing age, these variables accounted for only a small proportion of the variance in VT. These data suggest that VT determinations are a useful method for quantifying sensory abnormalities in cancer patients. Sensory abnormalities occur in a significant proportion of patients with cancer and seem to be related directly to the neoplasm, rather than to known risk factors for neuropathy.     

Congenital fibre type disproportion with unusual clinico-pathologic manifestations.

Two cases with congenital fibre type disproportion are presented. The cases are unusual in that there were significant dysmorphic features in case 1, and both cases showed electromyographic abnormalities suggestive of denervation. A third case, the father of the second patient, showed clinical features of congenital fibre type disproportion in early life but later developed the rigid spine syndrome. The spinal cord of case 3 showed atrophy and degeneration of medial neuronal group in the lumbosacral segments. The clinical and pathological features in these cases further extend the view that congenital fibre type disproportion may be seen in a variety of patients.     

Gastric and small intestinal dysfunction in spinal cord injury patients

Fynne L, Worsøe J, Gregersen T, Schlageter V, Laurberg S, Krogh K. Gastric and small intestinal dysfunction in spinal cord injury patients.
Acta Neurol Scand: 2012: 125: 123–128.
© 2011 John Wiley & Sons A/S. Background – Many patients with spinal cord injury (SCI) suffer from constipation, abdominal pain, nausea, or bloating, and colonic transit times are prolonged in most. Gastric and small intestinal dysfunction could contribute to symptoms but remain to be described in detail. Also, it is obscure whether the level of SCI affects gastric and small intestinal function. Aim – To study orocecal transit time and gastric emptying (GE) in patients with SCI. Methods – Nineteen patients with SCI (7 ♀, median age 54 years) and 15 healthy volunteers (9 ♀, median age 32 years) were included. All were referred because of neurogenic bowel problems. Eleven patients had low SCI (located at conus medullaris or cauda equina) affecting only the parasympathetic nerves to the left colon and eight had high SCI (above Th6) affecting parasympathetic and sympathetic innervation. Subjects ingested a small magnetic pill that subsequently was tracked by the Motility Tracking System – MTS‐1 (Motilis, Lausanne, Switzerland). Results – Orocecal transit time was longer than normal both in individuals with high lesions (P < 0.01) and in individuals with low lesions (P < 0.01). Individuals with high lesions had slower GE than those with conal/cauda equina lesions (P < 0.05). Basic contractile frequencies of the stomach and small intestine were unaffected by SCI. Conclusion – Surprisingly, upper gastrointestinal transit is prolonged in subjects with SCI suffering from bowel problems, not only in subjects with cervical or high thoracic lesions but also in subjects with conal/cauda equina lesions. We speculate that this is secondary to colonic dysfunction and constipation.     

Selective type II fibre muscular atrophy in patients with osteoarthritis of the hip

The size and the distribution of type I and tye II fibres was determined in the gluteus maximus (21 cases), gluteus medius (56 cases) and tensor faciae latae (27 cases) muscles of patients with osteoarthritis of the hip. The patients were of both sexes, aged between 37 and 64 years (younger group) and between 65 and 78 years (older group). Autopsy material of the two comparable age groups and of a group of "normal" adults (aged 22-44 years) served as controls. It was shown statistically that the diameter of both types of fibres and the relative number of type II fibres diminished with progressing age. In patients with osteoarthritis the degree of the selective atrophy of type II fibres was significantly higher than in the control groups. The atrophy is interpreted as a consequence of diminished muscular activity. No neurogenic lesions were detected either in the muscles of the patients or in those of the control groups.     

Paraneoplastic sensory neuronopathy and spontaneous regression of small cell lung cancer

BACKGROUND: Spontaneous tumour regression in small cell lung cancer has previously been suggested in patients with paraneoplastic neurologic syndromes. Rare documentation of this event has occurred in the literature. CASE REPORT: The authors report a patient with anti-Hu associated paraneoplastic sensory neuronopathy who had a spontaneous regression of her small cell lung cancer. CONCLUSIONS: This case supports the hypothesis that anti-Hu neurologic syndromes are the consequence of a misdirected immune response to small cell tumours.