[Differential diagnosis of Parkinson's disease]. / Differenzialdiagnose des Morbus Parkinson.

For a long time the diagnosis of Parkinson's disease has been considered to be easy. The advantages in treatment in the last decennia have shown that a more sophisticated differentiation from certain syndromes, which will be shortly described, is mandatory in order to achieve optimal therapeutic responses and for giving a prognosis.

The syndrome of 'continuous muscle fiber activity.'.

A 7-year-old boy who suffered from increasing stiffness and contractures of the extremities had distally pronounced atrophy and absent tendon reflexes. Electromyography showed continuous electrical activity during rest, sleep, after intravenous injection of diazepam, and after peripheral nerve block. The H reflex was elicitable; the silent period after the reflex was absent. Histopathological examination of the peroneus muscle disclosed a marked preponderance of type I fibers and slight atrophy of the type II fibers. Electron microscopic examination of the endplates demonstrated a marked atrophy of the postsynaptic regions and widened synaptic clefts. After one year's treatment with phenytoin, 200 mg daily, the patient showed an almost normal muscle tone. As not all of these electrophysiological phenomena can be fully explained by disturbances of the nerve terminals or the endplates, a further anomaly proximal from the peripheral nerve block seems to have been present.

Visual evoked response abnormality in myoclonus epilepsy with large pupils. Occurrence in a family with acorpuscular myoclonus epilepsy.

Flash and pattern evoked responses were recorded from three siblings with myoclonus epilepsy who all had strikingly large pupils in daylight. Comparison with the visual evoked responses (VERs) of 15 normal and eight epileptic control subjects (including one with myoclonus epilepsy but normal pupils) disclosed a substantial reduction of the amplitude of the flash response as compared with the normal pattern response in these three patients. It is suggested that the VER constellation and the pupillary abnormality, together with the normal electroretinogram and diffusely distributed relative scotomas, were due to a ganglion cell loss in the retina.

Autonomic dysfunction in botulism B: a clinical report.

Nine cases of botulism B with preponderant effects upon cholinergic autonomic innervation are presented. Blurred vision and dry mouth were constant symptoms. Impairment of salivary and lacrimal secretion were detectable for months. In the absence of clinical signs, electromyographic studies did not reveal neuromuscular involvement. Administration of antitoxin in the late course of such cases is not recommended, but guanidine can be used. Doubt is cast upon a new clinical entity called "acute autonomic neuropathy."

Parkinson's disease in twins: a follow-up study.

OBJECTIVE: To reevaluate concordance rates in 9 monozygotic (MZ) and 12 dizygotic (DZ) twin pairs with PD 8 years after the initial study. BACKGROUND: Longitudinal investigations increase accuracy in clinical diagnosis of PD. METHODS: Follow-up by personal interview and clinical examination. RESULTS: Concordance rates were not different between MZ (3/9) and DZ (5/12) twin pairs at follow-up, even when PD-associated dementia and isolated postural tremor were considered diagnostic of familial Lewy body parkinsonism. Evaluation of medical history, personality traits, and blink rate did not reveal putative early or premorbid parkinsonism in 9 co-twins who were motor-asymptomatic during the follow-up interval. However, these co-twins had reduced semantic fluency in comparison with a healthy control group of similar age. None of 7 co-twins without motor signs who underwent PET investigation 6 years previously showed signs of extrapyramidal disease at follow-up, but verbal memory continued to be reduced in 5 of these co-twins. CONCLUSION: Based on concordance rates only, the findings in our twin sample do not support a major genetic impact for the motor expression of PD.

Parkinson's disease in twins.

Among nine monozygotic (MZ) and 12 dizygotic (DZ) twin pairs in which an index case had typical Parkinson's disease (PD) or PD with associated dementia, three MZ and three DZ pairs were concordant. Three of the six affected co-twins were first diagnosed during the study. Occurrence of PD in families of MZ and DZ index cases was more frequent than expected from population rates. The study underlines the need for personal examination using defined criteria in a cross-sectional twin study on PD. Although the study did not establish a major genetic impact in the etiology of PD, a genetic predisposition for the disease cannot be ruled out for some individuals.

Temperature dependence of normal sensory nerve action potentials.

Sensory conduction velocities of normal subjects are increasing linearly with rising temperature. The duration of the compound sensory action potentials recorded from the median nerve at the wrist and elbow shows a negative temperature coefficient. The peak-to-peak amplitude of these potentials increases from 22 degrees to approximately 26 degrees C and then decreases progressively again up to 36 degrees C. It is believed that this behavior is due to a combination of decreasing temporal dispersion, height and duration of the individual spike potentials.

Auditory brain-stem potentials studied with paired stimuli in normals.

Brain-stem auditory evoked potentials (BAEPs) to paired stimuli of various intervals were recorded using a subtraction technique to cancel the first and facilitate recognition of the second response. In a pilot series of 12 experiments, no latency change was encountered with paired click intervals (PCI) of 8 and 6 ms. Thirty healthy subjects were then investigated by presenting single and paired stimuli with a PCI of 4, 3.1, 2.3 and 1.5 ms at a repetition rate of 10/s to each subject. With diminishing PCIs, identification and latency measurement of waves IV and V became increasingly difficult because of marked amplitude reduction. Component III remained identifiable in all but two recordings and showed a statistically significant latency increase and amplitude reduction only when the stimuli were presented 1.5 ms apart. Component I did not show a consistent latency change with any PCI but its amplitude was significantly reduced with 4 ms PCI. These findings differ from those reported when using PCIs of 5 ms or more and when using single stimuli at a high repetition rate, where component V was the most stable. The alterations of evoked potentials found only with a PCI of 1.5 ms are probably of central origin.

Is Parkinson's disease of early onset a separate disease entity?

Two groups of patients suffering from Parkinson's disease were studied. The first group consisted of 23 patients with an onset age before 40 years; in the second group of 21 patients the onset was after age 50. The clinical findings and the course of the disease were very similar in each group. In spite of a longer disease duration in the patients with early onset of the disease there was no difference in motor impairment; the younger patients did better in mental testing and they were taking less dopaminergic medication. These differences are thought to be due to the age difference rather than to the existence of different disease entities. In the early onset group more familial cases (mostly affecting siblings) were found than in the older ones. The points in favour of there being a hereditary subgroup of early onset Parkinson's disease or of environmental factors causing the disease are reviewed.

Electrophysiological investigations in a case of cephalic tetanus.

In a case of cephalic tetanus the amplitudes and the latencies of the compound action potentials recorded from the facial muscles after stimulation of the facial nerve at the mastoid were not significantly different on the two sides. With repetitive stimulation at 30/sec a pathological facilitation was observed on both sides. The blink reflex bilaterally had normal latencies but the amplitudes of the reflex potentials were always significantly lower on the paretic side. It is concluded that facial palsy in cephalic tetanus is mainly due to a functional block of conduction in the course of the peripheral nerve whereas the disturbance of neuromuscular transmission probably has little importance in these cases.

Longitudinal differences of susceptibility to ischaemia in human sensory nerve fibres.

The effect on the median nerve of ischaemia induced by a tourniquet (at a pressure of 250 mm Hg) placed on the upper arm was investigated in 12 young volunteers. In 6 of these 12 persons a second cuff, applying the same pressure as the first, was placed on the mid-forearm. In both groups the decrease in sensory action potentials and in nerve conduction velocity was more rapid in the proximal than in the distal segments. No other difference was detected between the two groups. It is concluded that the pressure induced by the cuff was not responsible for the changes and it is suggested that this phenomenon is due to internodal lengths being greater in the proximal than in the distal segments.

Electromyographic findings in patients after recovery from peripheral nerve lesions and poliomyelitis.

Electromyography was performed in 10 patients 14 to 50 years after acute poliomyelitis and in 12 patients 6 to 16 years after a peripheral nerve lesion. All patients had made an almost complete recovery from initially severe paresis. In the poliomyelitis group the main finding was an increased mean action potential duration in all patients. In the patients with peripheral nerve lesions an increased frequency of spontaneous activity could be seen in 8 out of 10 and an increased mean action potential duration in 7 out of 9 patients during the initial phase. Six to 16 years later the main pathological results were a prolonged mean action potential duration (9 out of 12 patients) whilst increased spontaneous activity was detectable only in 3 out of 12 patients. In two patients all EMG findings were normal.

Paramyotonia congenita. A clinical, electrophysiological and histological study of 12 patients.

The present paper describes the clinical, electrophysiological and histological findings made in 12 patients belonging to 2 genealogical lineages in Switzerland, suffering from paramyotonia congenita. This is the first report of this disease in Switzerland. The myopathy, transmitted by autosomal dominant inheritance, is characterized by a typical past medical history and by the persistent contraction of the muscles of the face, arms and legs provoked by exposure to cold. Also of diagnostic importance are the myotonic reactions inducible at room temperature, such as percussion myotonia, active myotonia and paradoxical myotonia. During paramyotonic episodes provoked by exposure of the subjects in a refrigeration chamber, serum potassium concentrations remained within normal limits. Potassium loading producing serum levels above 6 mEq/1 in 2 patients gave rise to stiffness and weakness of the arms and legs, but no signs of paralysis. Induced hypokalemia in 3 cases caused no paramyotonic symptoms. Electromyographic recordings in 5 patients showed myotonic discharges, which disappeared upon cooling of the limb, giving way to progressive muscular stiffness. Histological, histochemical and electronmicroscopical examination of the muscle tissue revealed only diagnostically unspecific myopathological changes.

Therapeutic experience with the new dopamine agonist CU 32-085 in advanced Parkinson's disease.

Twenty patients with advanced progressing Parkinson's disease have been treated with the 8-alpha-ergoline CU 32-085 in combination therapy for 3 months. With a mean daily dose of 12.65 mg, CU 32-085 together with levodopa plus a decarboxylase inhibitor produced a significant reduction in akinesia, rigor and tremor. Adverse reactions were rare and mild; in one case the drug was discontinued because of dyskinetic movements. Many of the pre-existing side effects were reduced or eliminated, particularly the involuntary movements and the levodopa response swings. The compound was considered useful in the treatment of advanced, progressing Parkinson's disease.

Subclinical visual field defects in multiple sclerosis. Demonstration and quantification with automated perimetry, and comparison with visually evoked potentials.

Fourteen patients with definite but inactive multiple sclerosis (MS) and 17 normal controls were examined with the automated perimeter octopus. Most of the patients had subclinical visual field defects, typically consisting of patchy, shallow scotomata located mostly in an area of between 15 degrees and 30 degrees eccentricity. In 8 patients, more than 15% of the tested visual field of at least one eye was abnormal. The severity and extent of the defects was unrelated to a history of optic neuritis. When visually evoked potentials (VEPs) of these subjects were examined using a reversing pattern, no correlation was found in the MS patients between prolonged VEP latencies and the location, depth or extent of visual field defects. Since subclinical visual field defects may be found in MS patients with normal VEP latencies, automated perimetry can be helpful in diagnosing some cases.

Visual evoked potentials in acute occipital blindness. Diagnostic and prognostic value.

Pattern-evoked and flash-evoked responses were recorded from four patients with acute blindness due to occipital ischaemia. No responses could be obtained with pattern stimulation. Flash stimulation, however, yielded well-reproducible potentials in all four cases in spite of practically complete visual loss. In one patient vision recovered completely while the three others showed poor or minimal recovery in restricted visual field areas only. It is concluded that the flash method is not appropriate for differentiation of occipital blindness from psychogenic visual disorders. Furthermore, preserved flash-evoked potentials in the acute stage of occipital blindness cannot be taken as a reliable prognostic sign for visual recovery, as has been postulated by others. A possible extrastriate origin of these flash responses is discussed in view of recent theories on a second visual system.

Neuromyopathy during chronic amiodarone treatment. A case report.

Clinical, electrophysiological, and the nerve and muscle biopsy findings from a case treated with amiodarone are reported. Marked distal motor and sensory impairment and distal muscular atrophy were observed clinically. The electrophysiological examination revealed normal motor and sensory conduction velocities in the median nerve; the sensory action potentials were polyphasic and reduced in amplitude. Electromyography revealed denervation potentials and severe loss of motor units in the M. extensor digitorum brevis and in the M. tibialis anterior. The light and electronmicroscopical study of a N. suralis biopsy displayed total loss of large myelinated fibers and an almost total reduction of small myelinated fibers. The number of unmyelinated axons was markedly reduced. Fibrocytes and degenerative axons polymorphous inclusion bodies were present in Schwann cells. The muscle biopsy revealed both neurogenic and myopathic changes. Lipid storage was also present in the muscle fibers. Physical and chemical analysis of the nerve and muscle biopsy revealed the content of iodine to be more than 40 times increased. The findings indicate damage of axons, schwann cells and muscle fibers. It is suggested that the lipid storage in nerve and muscle tissue might be related to the accumulation of the drug or its metabolites.

Pattern reversal evoked cortical responses in normals. A study of different methods of stimulation and potential reproducibility.

Using a commercially available television set for stimulation of 78 healthy subjects, the upper limit of normal for the latency of the major positive wave (p 100) of checkerboard pattern reversal evoked potentials is practically the same as that obtained by employing slide projector combined with a rotating mirror. Potentials evoked by a small pattern, for purely foveal stimulation, were often difficult to evaluate exactly. Fixation of a large pattern at the upper border of the stimulus field brought no advantages as compared to the usual fixation in the center. Continuous prolonged recordings, with successive averaging of 64 pattern reversals, confirmed statements that only the major positive wave and its latency are constantly reproducible without being influenced by fatigue or inattention. Repeated examinations in the same subjects at intervals of 2 weeks showed a considerable spread of the latencies from one session to the other but the absolute values always ranged within the normal. More or less large latency differences (up to 12ms with large pattern stimulation) were found in every subject at least once. A longer latency found at a control examination, or a newly appearing latency difference, therefore do not prove a fresh optic nerve lesion as long as the absolute values are still within the limits of normal. From repeated examinations it could also be seen that foveal stimulation with a small pattern is not suitable for routine examinations because of high variation in the results.

Thalidomide-induced peripheral neuropathy. A prospective clinical, neurophysiological and pharmacogenetic evaluation.

Prospective clinical and electrophysiological follow-up was performed on nine patients under thalidomide treatment in order to detect the very beginning of possible drug-induced peripheral neuropathy. For neurophysiological assessment, nerve conduction measurements of the median, peroneal and sural nerves (7 conduction parameters) and needle EMG examination of the anterior tibial muscle were performed. The results of a first control after about 3 months of treatment were compared with the starting point examination, and the patients were then classified as "affected" or "not affected" according to clinical and neurophysiological criteria. At this point, three patients showed clinical and electrophysiological, and another two only electrophysiological alterations suggesting early neuropathy. This classification did not change after further clinical and electrophysiological controls. Without starting-point values, the early detection of neuropathy would not have been possible in all patients. No single reliable neurophysiological parameter for detection of thalidomide-induced neuropathy could be found. Pharmacogenetic classification with regard to hydroxylation and acetylation phenotypes was then performed in some patients and interpreted with relation to thalidomide neurotoxicity. A possible relationship between slow acetylators and development of thalidomide-induced neuropathy was found.

Autonomic disturbances and cardiovascular reflexes in idiopathic Parkinson's disease.

A total of 22 patients suffering from idiopathic Parkinson's disease and 20 age-matched volunteers were questioned about autonomic disturbances and all underwent four non-invasive tests examining cardiovascular reflexes. Significantly more autonomic disturbances were reported by the patients than by the controls. Resting blood pressure was significantly decreased in patients taking dopamine agonists, whereas it was normal in those patients who only received levodopa and anticholinergics. Resting heart rate and resting beat-to-beat variation were normal in the patients, as were the blood pressure response to standing and the postural heart rate response. No pathological response to the Valsalva manoeuvre could be detected. On the other hand, the heart rate variation evoked by deep breathing as well as the blood pressure response and the heart rate response to sustained isometric exercise were significantly diminished in the patients with idiopathic Parkinson's disease. These findings indicate a central disturbance of cardiovascular reflex control, whereas the corresponding peripheral pathways seem to be normal.