Esa Mervaala

Natural History of Peripheral Neuropathy in Patients with Non-Insulin-Dependent Diabetes Mellitus

BACKGROUND There is little information on the incidence and natural history of neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). METHODS We studied patients with newly diagnosed NIDDM and control subjects both at base line and 5 and 10 years later. Polyneuropathy was diagnosed on the basis of clinical criteria (pain and paresthesias) and electrodiagnostic studies (nerve conduction velocity and response-amplitude values). We investigated the relation between metabolic variables (results of oral glucose-tolerance tests, serum lipid and insulin concentrations, and glycosylated hemoglobin values) and the development of polyneuropathy. RESULTS In 10 years, 36 patients with NIDDM and 8 control subjects died; 86 patients and 121 control subjects completed the study. When the study ended, 18 percent of the patients were being treated only with diet, 59 percent with oral hypoglycemic drugs alone, 12 percent with insulin alone, and 11 percent with both insulin and oral hypoglycemic agents. At base line the prevalence of definite or probable polyneuropathy among the patients with NIDDM was 8.3 percent, as compared with 2.1 percent among the control subjects. These values 10 years later were 41.9 percent and 5.8 percent, respectively. The number of patients with NIDDM who had nerve-conduction abnormalities in the legs and feet increased from 8.3 percent at base line to 16.7 percent after 5 years and to 41.9 percent after 10 years. The decrease in sensory and motor amplitudes, indicating axonal destruction, was more pronounced than the slowing of the nerve conduction velocities, which indicates demyelination. Among the patients with NIDDM, those with polyneuropathy had poorer glycemic control than those without. Low serum insulin concentrations before and after the oral administration of glucose were associated with the development of polyneuropathy, regardless of the degree of glycemia. CONCLUSIONS The prevalence of polyneuropathy among patients with NIDDM increases with time, and the increase may be greater in patients with hypoinsulinemia.

Quantitative MRI of the hippocampus and amygdala in severe depression

BACKGROUND There is little evidence to support possible structural changes in the amygdala and hippocampus of patients with severe depression. METHODS Quantitative MRI of the amygdala and hippocampus, as well as proton spectroscopy (MRS) of mesial temporal structures were studied in 34 drug-resistant in-patients with major depression and compared with 17 age-matched controls. Volumetric MRI data were normalized for brain size. RESULTS The volume of the left hippocampus was significantly smaller in the patients compared with the controls. Both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The patients, but not the controls, had significant asymmetry of the amygdalar volumes (right smaller than left). No differences were observed between the patients and controls in the T2 relaxation times for the hippocampus and amygdala. Mesial temporal lobe MRS revealed a significantly elevated choline/creatine ratio in the patients compared with the controls. CONCLUSIONS This quantitative MRI study provides support for a possible association between structural and biochemical substrates and severe drug-resistant major depression.

Human brain connectivity during single and paired pulse transcranial magnetic stimulation

OBJECTIVE Intracortical inhibition (SICI) and facilitation (ICF) in the human motor cortex can be measured using a paired pulse transcranial magnetic stimulation (ppTMS) protocol. Recently, a technical device has been introduced, which allows recording electroencephalographic (EEG) responses to TMS of a given scalp site. The latency, amplitude and scalp topography of such responses are considered a reflection of cortico-cortical connectivity and functional state. The aim of the present study is to better characterize the neuronal circuits underlying motor cortex connectivity as well as the mechanisms regulating its balance between inhibition and facilitation by means of EEG navigated-ppTMS coregistration. METHODS Sub-threshold and supra-threshold single and ppTMS of the left primary motor cortex were carried out during a multi-channel EEG recording on 8 healthy volunteers; the between-pulse intervals used in the paired pulse trials were 3 (for SICI) and 11 ms (for ICF). Motor evoked potentials (MEPs) from the opposite hand were simultaneously recorded. RESULTS Single and ppTMS induced EEG responses characterized by a sequence of negative deflections peaking at approximately 7, 18, 44, 100 and 280 ms alternated with positive peaks at approximately 13, 30, 60 and 190 ms post-TMS. Moreover, ppTMS modulated both EEG evoked activity and MEPs. Amplitude variability of EEG responses was correlated with - and therefore might partially explain - amplitude variability of MEPs. INTERPRETATION EEG-ppTMS is a promising tool to better characterize the neuronal circuits underlying cortical effective connectivity as well as the mechanisms regulating the balance between inhibition and facilitation within the human cortices and the corticospinal pathway.

Long term outcome of temporal lobe epilepsy surgery: analyses of 140 consecutive patients

Objective: To analyse the long term results of temporal lobe epilepsy surgery in a national epilepsy surgery centre for adults, and to evaluate preoperative factors predicting a good postoperative outcome on long term follow up. Methods: Longitudinal follow up of 140 consecutive adult patients operated on for drug resistant temporal lobe epilepsy. Results: 46% of patients with unilateral temporal lobe epilepsy became seizure-free, 10% had only postoperative auras, and 15% had rare seizures on follow up for (mean (SD)) 5.4 (2.6) years, range 0.25 to 10.5 years. The best outcome was after introduction of a standardised magnetic resonance (MR) imaging protocol (1993–99): in unilateral temporal lobe epilepsy, 52% of patients became seizure-free, 7% had only postoperative auras, and 17% had rare seizures (median follow up 3.8 years, range 0.25 to 6.5 years); in palliative cases (incomplete removal of focus), a reduction in seizures of at least 80% was achieved in 71% of cases (median follow up 3.1 years, range 1.1 to 6.8 years). Most seizure relapses (86%) occurred within one year of the operation, and outcome at one year did not differ from the long term outcome. Unilateral hippocampal atrophy with or without temporal cortical atrophy on qualitative MR imaging (p < 0.001, odds ratio (OR) 5.2, 95% confidence interval (CI) 2.0 to 13.7), other unitemporal structural lesions on qualitative MR imaging (p ≤ 0.001, OR 6.9, 95% CI 2.2 to 21.5), onset of epilepsy before the age of five years (p < 0.05, OR 2.9, 95% CI 1.2 to 7.2), and focal seizures with ictal impairment of consciousness and focal ictal EEG as a predominant seizure type (p < 0.05, OR 3.4, 95% CI 1.2 to 9.1) predicted Engel I–II outcome. Hippocampal volume reduction of at least 1 SD from the mean of controls on the side of the seizure onset (p < 0.05, OR 3.1, 95% CI 1.1 to 9.2) also predicted Engel I–II outcome. Conclusions: Outcome at one year postoperatively is highly predictive of long term outcome after temporal lobe epilepsy surgery. Unitemporal MR imaging abnormalities, early onset of epilepsy, and seizure type predominance are factors associated with good postoperative outcome.

High-dose thiopental in the treatment of refractory status epilepticus in intensive care unit

The authors studied prospectively the effects of thiopental anesthesia on seizure control, hemodynamics, and the course of intensive care in 10 patients with refractory status epilepticus. Clinical and electrophysiological seizures were terminated in every patient. Hemodynamically, thiopental was well tolerated, but slow recovery from anesthesia prolonged the need for intensive care.

Motor potentials evoked by navigated transcranial magnetic stimulation in healthy subjects.

Summary: Navigated transcranial magnetic stimulation (TMS) is a tool for targeted, noninvasive stimulation of cerebral cortex. Transcranial stimuli can depolarize neurons and evoke measurable effects which are unique in two ways: the effects are caused directly and without a consciousness of the subject, and, the responses from peripheral muscles provide a direct measure for the integrity of the whole motor pathway. The clinical relevance of the method has not always been fully exposed because localizing the optimal stimulation site and determining the optimal stimulation strength have been dependent on time-consuming experimentation and skill. Moreover, in many disorders it has been uncertain, whether the lack of motor responses is the result of true pathophysiological changes or merely because of unoptimal stimulation. We characterized the muscle responses from human primary motor cortex system by navigated TMS to provide normative values for the clinically relevant TMS parameters on 65 healthy volunteers aged 22 to 81 years. We delivered focal TMS pulses on the primary motor area (M1) and recorded muscle responses on thenar and anterior tibial muscles. Motor threshold, latencies and amplitudes of motor-evoked potentials, and silent period duration were measured. The correction of the motor-evoked potential latency for subjects’ height is provided. In conclusion, we provide a modified baseline of TMS-related parameters for healthy subjects. Earlier such large-scale baseline material has not been available.

Long-term epilepsy surgery outcomes in patients with MRI-negative temporal lobe epilepsy

Purpose:  The outcome of surgery in patients with temporal lobe epilepsy (TLE) and normal high‐resolution magnetic resonance imaging (MRI) has been significantly worse than in patients with unilateral hippocampal damage upon MRI. The purpose of this study was to determine the long‐term outcomes of consecutive true MRI‐negative TLE patients who all underwent standardized preoperative evaluation with intracranial electroencephalography (EEG) electrodes.

MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.

Effect of vigabatrin on epilepsy in mentally retarded patients A 7‐month follow‐up study

We studied the antiepileptic potency of vigabatrin (γ-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.

[18F]FDG-PET and whole-scalp MEG localization of epileptogenic cortex

Summary: Purpose: To evaluate combined [18F]fluorodeoxy‐glucose (18F‐FDG) positron emission tomography (PET) and 122‐channel whole‐scalp magnetoencephalography (MEG) in lateralizing the epileptogenic cortex in patients whose routine presurgical evaluations gave discordant results about the location of the epileptic focus.