J. De Bleecker

INTERMEDIATE SYNDROME IN ORGANOPHOSPHORUS POISONING - A PROSPECTIVE-STUDY.

Objectives:To estimate the frequency of the intermediate syndrome in organophosphoruspoisoned patients, and examine its relationship to cholinesterase inhibition and electromyographic findings. Muscle biopsies were available in some patients. Design:A 3-yr prospective study. Setting:University teaching hospital intensive care unit. Patients:Consecutive patients with acute organophosphorus poisoning (n = 19). Measurements and Main Results:We determined the frequency of the intermediate syndrome in poisonings with various organophosphates, duration of (acetyl) cholinesterase inhibition and metabolite excretion, evolution of alterations on repetitive nerve stimulation, type and frequency of muscle lesions. A total of eight of 19 patients developed an intermediate syndrome. In some patients, short relapses of muscarinic symptoms superimposed on the intermediate syndrome. Agents such as methylparathion, fenthion, and dimethoate carry a high risk, but we also noted a prolonged intermediate syndrome in an ethyl-parathion-poisoned patient. Prolonged and severe cholinesterase inhibition occurred during the intermediate syndrome in all patients, and metabolite excretion was prolonged. As the intermediate syndrome evolved, repetitive nerve stimulation initially demonstrated decrement, then increment, and finally, normal responses. Necrotic fibers were noted in muscle biopsies, but these fibers were too sparse to explain severe muscle weakness and were similar in patients with and without the intermediate syndrome. No patients developed delayed neuropathy. Conclusions:The intermediate syndrome is not rare. Although it is more likely to occur with some organophosphates, it is not confined to a few distinct compounds. This syndrome coincides with prolonged cholinesterase inhibition, and is not due to muscle fiber necrosis. When viewed together, the clinical and electromyographic features are best explained by combined pre- and postsynaptic dysfunction of neuromuscular transmission. The intermediate syndrome is not related to an incipient delayed neuropathy. (Crit Care Med 1993; 21:1706–1711)

Open-label trial of anti-TNF-alpha in dermato- and polymyositis treated concomitantly with methotrexate

Background/Aims: To determine the efficacy of infliximab combined with weekly methotrexate in drug-naive recent-onset dermatomyositis and polymyositis. Methods: A multicentre open-label controlled trial was conducted. Disease activity was assessed using patient’s and physician’s disease activity assessment, manual muscle testing (MMT), handheld dynamometry, and serum CK. The primary objective was to assess the efficacy using MMT after a period of 26 weeks. Results: The study was terminated prematurely because of a low inclusion rate and a high drop-out rate due to disease progression and the occurrence of an infusion reaction. The few patients who did reach the primary endpoint showed improvement in all aspects studied. Conclusion: Infliximab combined with weekly methotrexate might be safe and well tolerated in a small subgroup of patients with drug-naive recent-onset myositis. At present, we do not advocate the use of this treatment because treatment response cannot be predicted beforehand.

Differential Regional Cerebral Uptake of 18F-Fluoro-2-Deoxy-D-Glucose in Alzheimer’s Disease and Frontotemporal Dementia at Initial Diagnosis

In this paper, the cerebral uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) was studied in a relatively small group of patients suffering from either clinically diagnosed Alzheimer’s disease (AD) or frontotemporal dementia during the initial differential diagnostic workup. The image analysis was done visually and semiquantitatively using three different reference regions. Visual analysis confirmed earlier literature findings on the distribution of decreased FDG uptake and demonstrated prevalent asymmetric patterns in both groups. Only semiquantitative analysis using the sensorimotor cortex as a reference region confirmed the visual findings. Moreover, there were no differences in medial temporal lobe activities between both groups, and there was no correlation of medial temporal lobe activity with dementia severity. In the AD group, a correlation of parietal FDG uptake with MMSE scores was found.

Successful immunoglobulin treatment in a patient with neuromyotonia.

Neuromyotonia is characterized by spontaneous and continuous muscle fibre activity leading to muscle cramps, pseudomyotonia, myokymia and weakness. Electromyographic recordings show typical findings. An auto-immune mechanism has been suggested in at least a subset of patients. Various therapies have been tried with different outcome. A patient with neuromyotonia responding well to high-dose immunoglobulin treatment is presented.

Peripheral lymphoid tissue-like adhesion molecule expression in nodular infiltrates in inflammatory myopathies

Non-granulomatous nodular accumulations of inflammatory cells in inflammatory myopathies were studied to characterize adhesion mechanisms used for leukocyte recruitment. The nodules had a B-cell-rich center surrounded by a helper T-cell-rich peripheral zone, resembling lymph nodes. The T-cell-rich zones harbored high-walled venules resembling high endothelial venules (HEV), whose endothelia frequently expressed ICAM-1, VCAM-1, and less constantly E-selectin. This endothelial adhesion molecule profile differs from that found in polymyositis, inclusion body myositis, or dermatomyositis, but resembles that in lymphoid tissues. Also, the peripheral lymph node addressin, a vascular addressin specific for peripheral lymphoid tissue HEV, was present on many HEV. This adhesion system is probably responsible for the excessive lymphocyte recruitment. The similar cellular organization and lymphocyte recirculation mechanisms of the nodular infiltrates in muscle and of lymph nodes suggest that the former may also produce antibodies.

Postsynaptic neuromuscular dysfunction in organophosphate induced intermediate syndrome

SummaryA 65-year-old Caucasian female developed an intermediate syndrome seven days after an acute cholinergic crisis, caused by the ingestion of fenthion.Cholinesterase activity in the blood, plasma and red cells was monitored daily by the method according to Nenner and serial serum fenthion levels were measured by capillary gas chromatography.Electromyographic studies showed fade on tetanic stimulation by means of surface electrodes at 20 Hz of the left M. abductor digiti quinti at day 7, which could no longer be observed at day 19.Fade on low-frequency stimulation and posttetanic facilitation were both absent.A biopsy of the N. suralis was normal. A biopsy of the M. tibialis anterior revealed a limited rhabdomyolysis with a very weak staining for cholinesterase.It is hypothesized that the pathophysiologic process underlying the syndrome is the result of a time-confined phenomenon, which includes both changes in the postsynaptic structures by a desensitization process and a gradually restoring ratio of acetylcholine to acetylcholinesterase. This hypothesis is suggested by the similarity in the EMG-findings of this patient and those in myasthenia gravis, which is known to be characterized by a postsynaptic transmission defect.

Intermediate syndrome due to prolonged parathion poisoning

A parathion‐poisoned patient with prolonged cholinesterase inhibition due to impaired hepatic metabolism and urinary excretion is reported. An intermediate syndrome characterized by respiratory paresis, weakness in the territory of several motor cranial nerves and of proximal limb and neck flexor muscles, persisted for 3 weeks. During this whole period, cholinesterase remained markedly reduced. Serial EMGs with repetitive nerve stimulation pointed to a combined pre‐ and postsynaptic disorder of neuromuscular transmission. Electron microscopy of an intercostal muscle biopsy showed focal degeneration at the poorly branched postsynaptic folds, and was considered to be nonspecific.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T > C

Background: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. Objectives: To determine the clinical–neurological spectrum and associated mutation loads in an extended m.14487T>C family. Methods: A genotype–phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. Results: Heteroplasmic m.14487T>C levels (36–52% in leucocytes, 97–99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99–100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. Interpretation: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Cobalt-55 positron emission tomography in late-onset epileptic seizures after thrombo-embolic middle cerebral artery infarction

The pathogenesis of late-onset epileptic seizures after thrombo-embolic cerebral infarction is poorly understood. Our previous positron emission tomographic (PET) studies with 15O have demonstrated that post-apoplectic epilepsy is associated with more severe brain ischemia, but we were unable to determine if this was the cause or the consequence of the seizures. Using cobalt-55 (55Co) as PET tracer we can now distinguish recurrent, recent infarction in patients with a previous old infarct in the same vascular territory. In seven out of twelve patients with post-apoplectic seizures an increased uptake of 55Co was observed in the border area and in two of them also within the old infarct core. In the control group, composed of eight seizure-free patients with also an old infarct involving the cortical territory of the middle cerebral artery, no increase in 55Co uptake was observed on PET examination. The present study indicates that in a significant number of patients late-onset epilepsy is the clinical expression of recurrent strokes, occurring in the same vascular territory.

Cobalt-55 positron emission tomography in recurrent ischaemic stroke

The present study investigates if Cobalt-55 (55Co) positron emission tomography (PET) allows us to distinguish and detect recent, recurrent strokes in patients who had already suffered a previous infarct in the same vascular territory. Fourteen patients with recurrent strokes underwent a 55Co PET scan of the brain. Recently infarcted areas, less than 2 months old, had a high 55Co uptake ratio, whereas infarcts of 6 months to 1 year had an uptake ratio comparable to normal brain tissue. In infarcts older than 2 years the 55Co uptake ratio was decreased compared to the control values. The evolution in 55Co uptake ratios with time can be explained by the dynamics of the inflammatory response within the infarct core. 55Co PET allows to demonstrate stroke recurrence and suggests that single photon emission tomography, using 57Co as the tracer, could be a more easy alternative to be used in routine neurological practice.