Sweating impairment in patients with multiple sclerosis.

OBJECTIVES: To measure sweating in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Sweating was measured by an evaporimeter after a heating stimulus in 29 MS patients and in 15 healthy control subjects. RESULTS: The MS patients sweated markedly less than the controls. After 10 min of heating the sweating was significantly lower in the forehead (P = 0.034), feet (right, P = 0.033; left, P = 0.037) and legs (right, P = 0.043; left, P = 0.029) of the MS patients than in those of the controls. After 15 min of heating the difference was statistically significant only in the feet (right, P = 0.043; left, P = 0.029). The Expanded Disability Status Scale score correlated inversely with sweating at 15 min of heating in the left hand (r = 0.42, P < 0.05), and in the left (r = 0.36, P < 0.05) and right foot (r = 0.37, P < 0.05). CONCLUSIONS: MS is associated with an impairment in thermoregulatory sweating which seems to be related to the disease severity.

Sympathetic skin responses in multiple sclerosis.

OBJECTIVES: This study assessed the sympathetic skin responses (SSRs) and their correlation with brain lesion volumes in patients with multiple sclerosis (MS). MATERIALS AND METHODS: The SSRs were measured in 27 patients with MS and 27 healthy controls. The volumes of the proton density-weighted MS lesions in the brain were measured using MRI. RESULTS: The SSRs were abnormal in 52% of the patients with MS, but absent only in clinically severe MS. The total lesion volume in the whole brain correlated significantly with both the severity of MS expressed by the EDSS score (P < 0.001) and the decreased SSR amplitudes in the feet (P < 0.01). Focal lesion volumes in the temporal lobe (P < 0.01), in the pons (P < 0.01) and in the cerebellum (P < 0.01) were also separately associated with abnormal SSR reflexes. CONCLUSIONS: Sudomotor regulation failure in MS is associated with certain focal MS lesions.

Peripheral nerve function is increasingly impaired during puberty in adolescents with type 1 diabetes.

OBJECTIVE: To evaluate the impact of puberty on peripheral nerve function in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Of 138 eligible patients with type 1 diabetes, 100 patients (age >9 years and diabetes duration >2 years) attending an outpatient diabetes clinic and 100 age- and sex-matched healthy control subjects took part in this cross-sectional study. Peripheral motor and sensory nerve conduction tests, cardiovascular reflex tests on the autonomic nervous system, and measurements of vibration-perception threshold (VPT) were performed. RESULTS: Nerve conduction velocity (NCV) in the distal motor and sensory nerves, the motor nerve distal latency, and the sensory nerve action potential (SNAP) amplitude were impaired in the adolescent patients with type 1 diabetes. The deterioration in motor NCV, H-reflex latency, and SNAP amplitude became more conspicuous in late puberty and postpuberty and was related to poor metabolic control. A total of 10 patients had distal diabetic polyneuropathy (DP) neurophysiologically, and these patients had significantly lower heart-rate variation in the deep breathing test than the other patients. Three of the patients with DP had peripheral neurological signs or symptoms. A slight difference in the VPT between the patients and control subjects was observed after puberty. CONCLUSIONS: Increasing subclinical motor nerve impairment can be detected during late puberty and after puberty, and sensory NCV and SNAP amplitude are reduced in adolescents with type 1 diabetes. Poor metabolic control during puberty appears to induce deteriorating peripheral neural function in young patients with type 1 diabetes.

Changes in collagen metabolism in diseased muscle. II. Immunohistochemical studies.

Immunofluorescence studies using specific antibodies against collagen of types I, III, IV, and V were carried out on muscle biopsy specimens from 22 patients with various neuromuscular disorders and seven controls. Increased staining with all antibodies was seen in the patients with polymyositis and muscular dystrophy. Increased staining with types I and III antibodies was found in the samples from the patients with amyotrophic lateral sclerosis in cases with an elevated concentration of muscular hydroxyproline. Two patients with amyotrophic lateral sclerosis showed no accumulation of collagen, and this was similarly true of the polyneuropathy cases. An accumulation of types IV and V collagen was typical for the myotonia congenita samples. The immunohistochemical results were in good agreement with the biochemical findings from the same patients.

Changes in collagen metabolism in diseased muscle. I. Biochemical studies.

Possible changes in collagen biosynthesis were studied in 50 patients with neuromuscular disorders and 14 controls. Type III procollagen aminoterminal propeptide concentrations and galactosylhydroxylysyl glucosyltransferase (GGT) activities were assayed in serum, and prolyl 4-hydroxylase and GGT activities were assayed in muscle biopsy specimens. All four assays showed significantly elevated values in cases of polymyositis, adult forms of muscular dystrophy, and amyotrophic lateral sclerosis, the concentration of muscular collagen also being significantly increased in the last two conditions. Some abnormalities were also seen in polyneuropathy, myotonia congenita, and undefined myopathy. High correlations were found among the values for the four assays, but no marked correlations with muscular collagen concentration or enzyme activities characteristic of neuromuscular disorders were found. The four assays may reflect changes in actual collagen synthesis in the diseased muscle.

Muscle-specific carbonic anhydrase III is a more sensitive marker of muscle damage than creatine kinase in neuromuscular disorders.

Serum concentration of carbonic anhydrase III (S-CA III), a novel marker of type I skeletal muscle cells was measured in 37 patients with neuromuscular diseases (polymyositis, muscular dystrophies, amyotrophic lateral sclerosis, and other neurogenic diseases) and in 24 control patients. Significant elevation in S-CA III was observed in all patient groups. Serum concentration of carbonic anhydrase III correlated positively with serum-creatine kinase. Serum concentration of carbonic anhydrase III was observed to be a more sensitive skeletal muscle marker both in myogenic and in neurogenic muscle affecting diseases than serum creatine kinase.

Lysosomal and nonlysosomal hydrolases of skeletal muscle in neuromuscular diseases.

The activities of four lysosomal and two nonlysosomal hydrolases were studied in skeletal muscle biopsy samples from patients with neuromuscular diseases and from controls. beta-Glucosaminidase activity was increased in polymyositis. beta-Glucuronidase and alkaline protease activities were elevated in muscular dystrophy in adults, whereas cathepsin D activity was increased in amyotrophic lateral sclerosis. There were significant correlations between the activities of lysosomal and nonlysosomal hydrolases. The activity of beta-glucuronidase, beta-glucosaminidase, alkaline protease, and dipeptidyl aminopeptidase IV showed a positive correlation with the severity of muscular atrophy. The activities of these hydrolases and the activity of dipeptidyl aminopeptidase I correlated positively with the activities of muscular galactosylhydroxylysyl glucosyltransferase and with the serum concentration of type III procollagen aminoterminal propeptide. The results suggest that in neuromuscular diseases the lysosomal and nonlysosomal pathways for muscle degradation are affected concomitantly with collagen biosynthesis.

Selegiline diminishes cardiovascular autonomic responses in Parkinson's disease.

Selegiline (L-deprenyl), a selective inhibitor of monoamine oxidase type B, is an established adjuvant to levodopa therapy in Parkinson's disease (PD). To evaluate whether selegiline also effects the severity and progression of autonomic nervous system dysfunction in PD, we studied autonomic functions by measuring cardiovascular responses to normal breathing, deep breathing, the Valsalva maneuver, the tilting test, and the isometric contraction test prospectively in 52 PD patients receiving either selegiline (n = 27) or placebo (n = 25) in randomized order in a double-blind parallel trial. The study also continued double-blind after the introduction of levodopa. Recordings of cardiovascular responses were carried out annually, with the median follow-up period being 6 years. Cardiovascular autonomic reflexes were diminished in the patient groups compared with those of healthy control subjects (n = 45). There was no progression (except age-related) in dysautonomia in patients on placebo, but there was a decrease in cardiovascular responses in the selegiline group. The heart rate variability in normal breathing, in the Valsalva maneuver, and in the tilting test was clearly diminished during the selegiline treatment. In addition, in the tilting test, the fall in diastolic blood pressure immediately after tilting and in systolic blood pressure 2 minutes after standing up was more pronounced in the selegiline group than in the placebo group. Levodopa treatment had no effect on the measured autonomic responses. In the isometric contraction test, the two treatment groups showed no difference. We conclude that selegiline treatment diminishes autonomic responses, especially those of the sympathetic division. This sympatholytic effect may signal an increased risk of orthostatic hypotension.

Central and peripheral nervous system dysfunction in the clinical variation of Salla disease.

OBJECTIVE: To evaluate the degree of possible peripheral nervous system (PNS) involvement in addition to CNS manifestations in Salla disease, a free sialic acid storage disorder leading to severe mental retardation with a wide clinical variation. BACKGROUND: Salla disease is a lysosomal storage disorder that affects the white matter of the CNS. MRI findings and recent 1H MRS study results provide evidence for delayed central myelination, but there is no previous evidence for PNS involvement in this disease. The gene coding for a presumptive sialic acid transport protein has recently been identified, and the first disease-causing mutations have been characterized. METHODS: Nerve conduction studies; evoked potentials to visual (VEP), brainstem auditory (BAEP), and somatosensory stimuli (SEP); and EEG were carried out on 22 patients (age range 2 months to 57 years) with biochemically and genetically confirmed Salla disease. Brain MRI were available on 14 patients. RESULTS: Nerve conduction studies revealed abnormalities in nearly half of the patients (10/21). The four severely disabled patients and the oldest patient had greatly reduced nerve conduction velocities and prolonged distal latencies compatible with demyelinating polyneuropathy. In addition, SEP was abnormal in the majority of the patients, but VEP and BAEP in only a few cases. PNS involvement was clearly associated with both the phenotypic severity and MRI findings. CONCLUSIONS: The results indicate that dysmyelination in Salla disease occurs not only in the CNS but also in the peripheral nervous system, contributing to the phenotypic variation, which can now be correlated with the molecular basis of the disease.

Demyelinating polyneuropathy in a patient with the tRNA(Leu)(UUR) mutation at base pair 3243 of the mitochondrial DNA.

A novel feature of demyelinating polyneuropathy was observed in a patient with the tRNA(Leu(UUR)) mutation at base pair 3243 of the mitochondrial DNA. Based on electrodiagnostic examination, the polyneuropathy was defined as being of the demyelinating, mixed (motor more than sensory) type. In a 1-year follow-up we observed approximately 7% reduction in both the motor and sensory conduction velocities. The other clinical features of the proband included a mild to moderate cognitive impairment and a combined hearing loss with a moderate sensorineural component. The proportion of the mutant genome found in the muscle of the proband was 29%, but the mutation was not found in his blood. A wide variability of the clinical phenotype was observed in the family of the proband. Heteroplasmic mutation was detected in the blood of most family members. The proportion of abnormal mitochondrial DNA was highest in the proband's brother, who had clinically definite mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, while the mutant genome was less frequent or absent in the subjects with less severe phenotypes and in healthy individuals. The findings on this pedigree emphasize the need for studies of complete families in the search for new clinical phenotypes of mutations in mitochondrial DNA.

Ubiquinone and nicotinamide treatment of patients with the 3243A-->G mtDNA mutation.

The efficacy and safety of ubiquinone (Q10) and nicotinamide were evaluated in a 6-month open-label trial in patients with the 3243A-->G mitochondrial DNA mutation. Blood lactate and pyruvate concentrations decreased, but there was little clinical improvement. Q10 and nicotinamide were well tolerated, but two patients died suddenly and unexpectedly during the trial. These deaths may have been unrelated to treatment. The unpredictable course of the disease makes evaluation of the clinical response difficult.

Effect of reinnervation on collagen synthesis in rat skeletal muscle.

The effect of reinnervation on the activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, and on the concentration of hydroxyproline (Hyp) was studied in gastrocnemius, soleus, and tibialis anterior muscles of rat 19, 26, 40, and 61 days after crush denervation of the sciatic nerve. The GGT activity was elevated in denervated gastrocnemius and soleus muscles and the PH activity in gastrocnemius. Muscular Hyp concentration was increased in denervated tibialis anterior muscle. Both the PH and GGT activities and the Hyp concentration returned to the control level during the reinnervation period (19-61 days from the start of denervation). It seems that denervation atrophy of skeletal muscle is associated with an increased rate of muscular collagen biosynthesis and that during reinnervation collagen synthesis rate decreases despite accelerated muscular growth. The results thus suggest that innervation is a powerful suppressive regulator of muscular collagen biosynthesis.

Effects of pregnancy on mothers' sleep.

OBJECTIVES: To survey the effects of pregnancy on mothers' sleep. METHODS: Mothers were interviewed during and after pregnancy with a series of five questionnaires to assess alterations in their sleep. The first questionnaire covered the 3 months before becoming pregnant, the next three the trimesters of pregnancy and the last the 3 months after delivery. The study was carried out in a central hospital and the maternity care units in the nearby rural community. Altogether, 325 pregnant women completed all five questionnaires. RESULTS: The total amounts of reported sleep and of nocturnal sleep increased significantly during the first trimester of pregnancy, began to decrease thereafter and were shortest during the 3 months after pregnancy. During late pregnancy expectant mothers over 30 years of age reported less sleep than those under 30. During the whole pregnancy, but increasingly toward the end of pregnancy, sleep became more restless and fragmentary and its subjective quality worsened, due at least partly to increased restless legs and nightly awakenings increasing with advancing pregnancy. CONCLUSIONS: The subjective quality of sleep is disturbed as early as the first trimester of pregnancy, although total sleeping time increases. The amount of reported sleep begins to decrease in the second trimester. The frequency of reported sleep disturbances, such as restless legs syndrome and nocturnal awakenings, is maximum in the third trimester but is about normal within 3 months after delivery.

Levodopa, bromocriptine and selegiline modify cardiovascular responses in Parkinson's disease.

Autonomic nervous system (ANS) involvement is frequently found in Parkinson's disease (PD), but its causal relationship to the disease itself and its medication is unclear. We evaluated the effects of PD medications on cardiovascular ANS functions. Heart rate (HR) responses to normal and deep breathing, the Valsalva manoeuvre and tilting, and blood pressure (BP) responses to tilting and isometric work were measured prospectively in 60 untreated PD patients randomised to receive either levodopa (n = 20), bromocriptine (n = 20) or selegiline (n = 20) as their initial treatment. The results were compared with those of 28 healthy controls. The responses were recorded at baseline, after 6 months on medication and following a 6-week washout period. At baseline HR responses to normal breathing, deep breathing and tilting were already lower and the fall in the systolic BP immediately and at 5 min after tilting was more pronounced in the PD patients than in the controls. Six months' levodopa treatment diminished the systolic BP fall after tilting when compared to baseline, whereas bromocriptine and selegiline increased the fall in systolic BP after tilting and selegiline diminished the BP responses to isometric work. The BP responses returned to the baseline values during the washout period. The drugs induced no change in the HR responses. Thus PD itself causes autonomic dysfunction leading to abnormalities in HR and BP regulation and the PD medications seem to modify ANS responses further. Bromocriptine and selegiline, in contrast to levodopa, increase the orthostatic BP fall and suppress the BP response to isometric exercise reflecting mainly impairment of the sympathetic regulation.

Motor evoked potentials of subjects over 70 years of age with and without recurrent falls.

Motor evoked potentials (MEPs) of 83 elderly (79+/-4 years) subjects, 43 with recurrent falls and 40 without, and of 31 healthy young (42+/-9 years) subjects were measured from thenar (and hypothenar) and tibialis anterior muscles. Forty-four of the aged subjects without overt neurological diseases were used as controls. Absolute latencies from the cortex to the target muscles as well as the latency differences from the cortex to the level of the fifth lumbar vertebra (LV) were longer in the aged than in the young, but the latency difference from the cortex to the brachial plexus was shorter. The cortical, brachial plexus and lumbar (LV) latencies were all dependent on height as well as age. The latency differences from the cortex to the plexus or LV were not height-dependent but were age-dependent. The thenar MAXMEP/CMAP ratio was significantly higher in hands with thenar atrophy (in 30% of the aged subjects) than without; thenar atrophy thus excludes the use of this parameter in about one-third of the aged subjects. There were no significant differences in the MEP latencies or amplitudes of the recurrent fallers and the non-fallers. Subjects having more frequent falls, however, tended to have lower amplitudes of MEPs in the lower extremities.

Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS.

OBJECTIVE: The aim of the present study was to investigate the cardiovascular autonomic control in clinically definite multiple sclerosis (MS) patients with a standardised battery of cardiovascular tests and to correlate these findings with the brain magnetic resonance imaging (MRI) lesion load. METHODS: Fifty-one patients with MS and 50 healthy controls were studied. Brain MRI was performed in all patients showing typical MS lesions. The cardiovascular tests were carried out using a standardised battery. RESULTS: Heart rate (HR) responses to deep breathing (P < 0.05) and tilt table testing (P < 0.001) were significantly decreased in MS patients when compared to those of the controls. Blood pressure (BP) responses in the tilt table test were also impaired in MS patients (diastolic P < 0.001, systolic P < 0.05). Of the different brain areas investigated the total volume of the midbrain MRI lesions (P < 0.05) was the one most clearly associated with the impaired BP responses. CONCLUSIONS: MS results in both reduced HR variation and decreased BP reactions indicating disturbed cardiovascular regulation. In particular, the midbrain lesions found in MS are associated with cardiovascular dysfunction.

Snoring and obstructive sleep apnea in children: a 6-month follow-up study.

BACKGROUND: Snoring children may present symptoms suggestive of obstructive sleep apnea syndrome (OSAS). Different and controversial methods to establish the diagnosis and to choose the treatment modalities have been proposed. OBJECTIVES: To study children with symptoms raising the suspicion of OSAS with overnight polysomnography (PSG). To evaluate the efficacy of adenotonsillectomy as treatment of pediatric OSAS and to elucidate the natural history of OSAS and primary snoring. DESIGN: A controlled, prospective, nonrandomized clinical trial. SETTING: Academic medical center. SUBJECTS: Fifty-eight snoring but otherwise healthy children aged 3 to 10 years with symptoms suggestive of OSAS underwent PSG twice, 6 months apart. Thirty healthy children served as controls. RESULTS: Twenty-seven children had OSAS with an obstructive apnea/hypopnea index greater than 1, while 31 had primary snoring. There were statistical differences in the symptoms and signs among the 3 study groups. Adenotonsillectomy was curative in the 21 children with OSAS who were operated on. Obstructive apneas and hypopneas in the healthy, nonsnoring children were almost nonexistent in this study. CONCLUSIONS: Half of the children or fewer with symptoms suggestive of OSAS actually had the condition. Clinical symptoms may raise the suspicion, but it is not possible to establish the diagnosis without PSG. Because snoring and obstructive symptoms may resolve over time, a normal PSG finding may help the clinician decide on an observation period. Adenotonsillectomy is curative in most cases of pediatric OSAS. Obstructive symptoms may continue after adenoidectomy alone.

Vincristine therapy for children with acute lymphoblastic leukemia impairs conduction in the entire peripheral nerve.

Somatosensory evoked potentials were measured prospectively in 38 children with acute lymphoblastic leukemia to evaluate the side effects of vincristine therapy on conduction of the peripheral nerves. Nineteen patients at standard risk received vincristine 12 mg/m2 during induction therapy and 19 patients at intermediate or high risk received 6 mg/m2 during induction therapy and an additional 6 mg/m2 during delayed intensification therapy. These latencies were compared with those of 38 age-, height-, and sex-matched controls. A prolongation in the peripheral conduction time of the posterior tibial nerve was found in the standard risk patients after induction compared with that of the controls, and a delay was found not only from the ankle to the popliteal fossa, but also from the popliteal fossa to the spinal cord (P < .01). The conduction times of the median nerve from the wrist to the plexus (P < .01) and from the wrist to the spinal cord (P < .01) were prolonged after delayed intensification therapy. There was a significant delay in the median and tibial nerve conduction between the intermediate and high risk patients and their controls after a total vincristine dose of 12 mg/m2. These delays were found along the entire length of the nerves, especially in the proximal part of the tibial nerve (P < .001).

Comparison of heart rate variability analysis methods in patients with Parkinson's disease.

The aim of the present study was to evaluate different analysis methods for revealing heart rate variability (HRV) differences between untreated patients with Parkinson's disease and healthy controls. HRV in standard cardiovascular reflex tests and during a 10 min rest period were measured by time- and frequency-domain and geometrical and non-linear analysis methods. Both frequency- and time-domain measures revealed abnormal HRV in the patients, whereas non-linear and geometrical measures did not. The absolute high-frequency spectral power of HRV was the strongest independent predictor to separate the patients from the controls (p = 0.001), when the main time-domain and absolute frequency-domain measures were compared with each other. When the corresponding normalised spectral units, instead of the absolute units, were used in the comparison, the two best single measures for separating the groups were the 30/15 ratio of the tilting test (p = 0.003) and the max/min ratio during deep breathing (p = 0.024). When the correlations between the different measures were estimated, the time-domain measures, fractal dimension and absolute spectral powers correlated with each other. The frequency- and time-domain analysis techniques of stationary short-term HRV recordings revealed significant differences in cardiovascular regulation between untreated patients with Parkinson's disease and the controls. This confirms cardiovascular regulation failure before treatment in the early stages of Parkinson's disease. The HRV spectral powers, in absolute units, were the most effective single parameters in segregating the two groups, emphasising the role of spectral analysis in the evaluation of HRV in Parkinson's disease.

Nasalance scores in snoring children with obstructive symptoms.

OBJECTIVE: Snoring and the sleep apnea syndrome (OSAS) in children are usually caused by adenotonsillar hypertrophy, which may affect air escape into the nose and nasal resonance. A microcomputer-based system makes it possible to objectively determine whether the oral passage is adequately separated from the nasal passage during phonation. The score thus obtained is called nasalance. This study was conducted to verify whether there exists differences in nasalance between primary snorers and OSAS-children. DESIGN: Fifty-three habitually snoring children (31 boys), mean age 6.1 years (range 3.2-10.5 years), were subjected to overnight sleep polygraphy (PG) and nasalance measurements with the Nasometer 6200. The study was successfully repeated 6 months later on 36 children. RESULTS: Nineteen children had obstructive apnea-h ypopneaindex (OAHI)> 1 on overnight polygraphy (OSAS-children), while 32 were considered primary snorers (PS), (OAHI<1). No statistically significant difference in nasalance scores was found between the OSAS- and PS children. Both groups of children had somewhat higher mean nasalance values both for oral and nasal passage sentences than the normative values for Finnish speech. In general, the most habitual snorers had lower nasalance scores than the less frequently snoring children (P=0.05). Earlier adenoidectomy or palatine tonsillar size did not have a significant influence on the nasalance. Adenotonsillectomy did not affect the nasalance scores of the nine children operated on during the follow-up period. CONCLUSIONS: According to the present study, nasalance measurements cannot be used to predict the incidence of OSAS among snoring children.