n-Che Chu

Peripheral Neuropathy in Mitochondrial Encephalomyopathies

Seven patients with mitochondrial encephalomyopathies were studied for peripheral neuropathy by clinical, electrophysiological and pathological examinations. The clinical manifestation of neuropathy varied from asymptomatic to mild and moderate sensorimotor symptoms with painful paresthesia. Five patients (2 with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, and 3 with myoclonic epilepsy and ragged-red fibers, MERRF) had clinical symptoms and signs of polyneuropathy associated mainly with decreased amplitudes of the compound muscle or nerve action potentials in an electrophysiological study indicating axonal degeneration. Sural nerve biopsy from 1 MERRF patient, also confirmed an axonal degeneration with reduction of large myelinated fibers. Mitochondrial DNA analysis of the sural nerve from this patient showed a point mutation from A to G transition at the nucleotide position 8344 with 80% mtDNA mutation. The results of this study suggest that peripheral neuropathy is not uncommon in mitochondrial encephalomyopathies and is predominantly due to axonal degeneration.

Chronic Carbon Disulfide Encephalopathy

To understand central nervous damage after long-term exposure to carbon disulfide (CS2), 10 patients who had polyneuropathy with various neuropsychiatric symptoms in a viscose rayon plant were studied. Clinical and laboratory examinations including electroencephalography (EEG), brain computed tomography (CT), brain magnetic resonance images (MRI), and carotid duplex sonography were carried out. Clinically, headache, unpleasant dreams, memory impairment, fatigue, anorexia and emotional lability were common in these patients while 2 patients had stroke episodes. EEGs were all normal. Brain CT scan showed mild cortical atrophy in 3 and low density lesions in the basal ganglia in 3. Brain MRI studies also disclosed mild cortical atrophy in 4 and multiple lesions involving the basal ganglia and corona radiata in 4. Carotid duplex sonography revealed mild atherosclerosis with plaques (< 20% stenosis) of extracranial vessels in 6. However there was no significant difference in flow velocities and flow volumes in the extracranial carotid arteries between patients and the normal controls. Interestingly, 2 patients had multiple brain lesions in the subcortical white matter but without strokes. In conclusion, encephalopathy with possible strokes may occur after chronic exposure to CS2, as well as polyneuropathy. The lesions usually involve the basal ganglia and subcortical white matter. Furthermore, MRI study may detect brain lesions particularly in the subcortical white matter areas before the occurrence of stroke.

Polyneuropathy induced by carbon disulphide in viscose rayon workers.

OBJECTIVES--To understand the prevalence of polyneuropathy and correlations among the clinical manifestations, electrophysiological findings, and degree of exposure to carbon disulphide (CS2) in workers who were exposed to variable concentrations of CS2 in a viscose rayon factory. METHODS--All the 163 workers received a detailed physical and neurological evaluation. Fixed point air samples were analysed for CS2. Nerve conduction velocity was studied in 26 workers with symptoms similar to neuropathy. RESULTS--Nine workers (53%) with overt polyneuropathy from the fibre cutting department and 19 workers (13%) with oligosymptoms similar to polyneuropathy from various jobs were noted. The fixed point air concentrations of CS2 were 150-300 ppm in the cutting areas and 15 to 100 ppm in the spinning areas. The estimated eight hour time weighted averages in the fibre cutting areas were 40-67 ppm. The occurrence of polyneuropathy was generally correlated with the degree of exposure to CS2. Nerve conduction velocities (NCVs) were significantly different in the overt polyneuropathy and subclinical polyneuropathy groups from the normal controls. The sensitive indicators for CS2 polyneuropathy were distal latency, motor NCV, and amplitude of sensory nerve action potentials in sensory NCVs. CONCLUSION--The outbreak of polyneuropathy was attributed to higher concentrations of CS2 in fibre cutting areas. Even in other jobs with relatively lower concentrations of CS2, the hazard of subclinical polyneuropathy cannot be overlooked.

Carbon disulfide induced polyneuropathy: sural nerve pathology, electrophysiology, and clinical correlation

We report the clinical features, electrophysiological studies, sural nerve pathology and recovery course of carbon disulfide‐(CS2) induced polyneuropathy in a 48‐year‐old man who worked in a viscose rayon plant. Sural nerve biopsy 2 years later still showed degeneration of both axon and myelin with a predominant loss of large myelinated fibers and remyelination. Electrophysiologic studies revealed mixed axonal and demyelinating polyneuropathy. To our knowledge, this is the first human report of sural nerve pathology in the recovery stage due to CS2 intoxication. After diagnosis, the patient was removed from the toxic environment. In the following three years, he showed part recovery predominantly in motor function compatible with the serial nerve conduction studies. We conclude that CS2 polyneuropathy may partly recover years after cessation of exposure.

Neurological Complications of Acute Intermittent Porphyria

Background: Acute intermittent porphyria (AIP) is an inherited disorder of heme biosynthesis, the clinical manifestations of which are incompletely understood. In this report, we describe 12 cases of AIP, focusing on the neurological manifestations. Methods: Twelve patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogen deaminase (PBGD) activity, and molecular genetics. Central and peripheral nervous system manifestations were noted, and electrophysiological and radiological studies performed. Potential precipitating factors were recorded. Results: Eleven PBGD gene mutations were identified in 12 patients. Nine patients experienced neurological symptoms involving the central nervous system (consciousness disturbance, n = 8; convulsion/seizure, n = 4; behavior change, n = 1), while 7 patients experienced peripheral neuropathies (motor paresis, n = 7; impairment of bulbar or respiratory function, n = 4). The electrophysiological and electroencephalographic findings were consistent with the neurological symptoms of AIP. Urinary PBG and δ-aminolevulinic acid levels were elevated in all patients. PBGD enzyme activity levels were below normal in all patients. Eight patients had documented exposure to porphyrogenic agents. Conclusions: Our detailed description of a relatively large number of cases of AIP may help clinicians to recognize this often difficult-to-diagnose disorder.

Clinical course in patients with chronic carbon disulfide polyneuropathy

The natural course of clinical manifestations and electrophysiological changes were studied in six patients with carbon disulfide (CS(2)) induced polyneuropathy. All of the six patients worked in the cutting-machine department of a viscose rayon plant. The environmental monitoring was also conducted in the initial stage and followed up 3 years later. In the 3-year follow-up period, the neurological symptoms and signs persisted. The highest concentration of CS(2) in the cutting machine where these patients worked was about 100-200 ppm. Three years later, the highest concentration was decreased to between 10 and 20 ppm in the cutting machine of the new production line after the engineering control had been improved. Nerve conduction velocity (NCV) studies revealed persistent abnormality in motor and sensory NCVs. Although, a tendency to improvement was noted, it did not reach a statistical significance except for conduction velocity of sural nerve in sensory NCV. Sural nerve biopsy from one patient, 2 years after diagnosis showed degeneration of both axon and myelin and a predominant loss of large myelinated fibers. A remyelination process was also noted. We concluded that CS(2) intoxication may induce a persistent damage to the peripheral nerves even after CS(2) exposure had ceased for 3 years.

Carbon Disulfide Vasculopathy: A Small Vessel Disease

We present the clinical manifestations of 4 male patients with acute stroke-like symptoms and polyneuropathy after long-term exposure to carbon disulfide (CS2) in a viscose rayon plant. The ages of onset of polyneuropathy ranged from 42 to 45 years with a duration of CS2 exposure between 6 and 21 years. The ages of onset of stroke were from 42 to 48 years. The risk factors for stroke including heart disease and diabetes were denied, except for smoking in 4, hyperlipidemia in 2 and hypertension in 1. At the initial visit in 1992, only 2 patients developed sudden onset of hemiparesis suggesting a lacunar stroke before the diagnosis of CS2 intoxication. Brain computed tomography (CT) scans showed low-density lesions in the basal ganglia in 2 patients, cortical atrophy in 1 and normal in 1. Brain magnetic resonance image (MRI) study disclosed multiple lesions in the corona radiata and basal ganglia on T2-weighted images in 3 patients and cortical atrophy in 1. After the diagnosis, they left their jobs for a CS2-free environment, and improvement of the working conditions was noted. During 5 years follow-up period, another 2 patients also developed an acute episode of stroke with hemiparesis. Brain CT and/or MRI follow-up studies in these 2 patients revealed new lesions in the basal ganglia and corona radiata. Intriguingly, a patient with previous stroke also developed new lesions in the bilateral thalami and brainstem. Carotid Doppler scan, transcranial Doppler scan and/or cerebral angiography did not show any prominent stenosis or occlusion in the major intracranial large arteries. We conclude that encephalopathy may occur in patients after long-term CS2 exposure, probably due to impaired cerebral perfusion. The lesions tend to occur in the basal ganglia, corona radiata and even brainstem, particularly involving the small-sized vessels. In addition, the cerebral lesions may progress even after cessation of CS2 exposure. Therefore, we suggest that CS2 exposure may be a risk factor for stroke.

Sensory Neuropathy due to Bajiaolian (Podophyllotoxin) Intoxication

Podophyllin, a herbal medicine known as Bajiaolian in Taiwan is the dried resin from the roots and rhizomes of Podophyllum peltatum. It has been applied as cathartic, helmintic and ointment for a variety of tumors and anogenital condylomata. The clinical manifestations include diarrhea, nausea, vomiting, tachycardia, oliguria, paralytic ileus, peripheral neuropathy, confusion, coma and even death [1, 2]. Podophyllotoxin is cytotoxic by arresting cellular mitosis in metaphase, inhibiting microtubule formation and increasing assembly of neurofilaments very similar to colchicine-like effects [3]. This toxin may involve the peripheral nervous system as well as the central nervous system (CNS) [4–6]. However, most studies are based on clinical observations and electrophysiological examinations [5–8]. Pathological studies on the peripheral nerves and the relationship between neurophysiological alterations and pathological changes in humans are rare [4, 7, 8].

Coenzyme Q10 treatment in Leber's hereditary optic neuropathy

The clinical manifestations and molecular genetic analysis of two patients with Lebers hereditary optic neuropathy (LHON) in a Taiwanese family are reported. A point mutation from G to A at the 11778th nucleotide position in the ND4 gene of mitochondrial DNA was found in the two probands.They were characterized by acute visual loss in the second or third decade of life.The clinical course was progressive in nature. Except for optic atrophy, there were no other neurological abnormalities. Intriguingly, a trial with coenzyme Q10 therapy for four months resulted in the rapid improvement of visual acuity in these two patients. To our knowledge, the prognosis of visual function is poor in LHON patients with the G11778A mutation. We conclude that, although spontaneous improvement may exist, coenzyme Q10 treatment may either be effective or speed up spontaneous improvement, particularly in the acute stage in the treatment of LHON patients.

Clinical phenotype and the G11778A mutation of mitochondrial DNA in patients with Leber’s hereditary optic neuropathy in Taiwan

We report the clinical manifestations and mitochondrial DNA (mtDNA) mutations of nine Chinese patients with Leber’s hereditary optic neuropathy from seven families in Taiwan. The nine probands were all males, aged 19 to 43 years at the time of the study and with ages of onset ranging between 13 and 30 years. They were characterized by an acute or subacute onset of visual loss in one eye, which progressed to the other eye within a few weeks. Their visual outcome was poor, although improvement was noted in four patients. A muscle biopsy from one patient showed a decreased activity of cytochrome c oxidase and subsarcolemmal mitochondrial aggregation. All patients and unaffected maternal family members had a homoplasmic G11778A mtDNA mutation regardless of variations in clinical manifestation. High frequencies of environmental factors such as smoking, alcohol consumption, trauma, and/or military training were found in these patients. We conclude that even though a homoplasmic G11778A mtDNA mutation was found in all patients and their maternal family members, this mutation could not account for the presentation of the clinical features. Additional genetic, epigenetic, and/or environmental factors may be important trigger factors in the clinical expression.