B. McNamara

Transcranial magnetic stimulation for depression and other psychiatric disorders

INTRODUCTION Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible alternative to electroconvulsive therapy for the treatment of selected patients with depression, bipolar affective disorder and schizophrenia. The aim of this study was to evaluate the evidence for the effectiveness of rTMS in mood disorders and schizophrenia. METHODS Studies were identified using MEDLINE (1966 to January 2000), EMBASE/Excerpta Medica (1980 to January 2000), Biological Abstracts and Index to Scientific and Technical Proceedings. A number of biomedical and TMS related websites were also searched. We estimated the number needed to treat to show beneficial effect of rTMS when compared with the placebo controlled group. RESULTS Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2-3 with a 95 % confidence interval 1.6 to 4.0, total; 81 patients. A single trial of rTMS has also been performed in mania, which shows a beneficial effect of right hemisphere stimulation when compared with left hemisphere stimulation. A controlled trial in schizophrenia failed to show any benefit of rTMS. DISCUSSION rTMS has demonstrable beneficial effects in depression. The extent and the duration of the anti-depressant effect of rTMS has yet to be defined. There now needs to be randomized controlled trials to compare rTMS directly with standardized electroconvulsive therapy in order to take this subject forward. With regard to the treatment of other mood disorders and schizophrenia, we are at an early stage in the assessment of further studies that are needed to examine any potential role for rTMS.

Clinical characteristics and outcome of patients diagnosed with psychogenic nonepileptic seizures: a 5-year review.

OBJECTIVE The goal of this article was to describe the clinical characteristics and outcomes of patients diagnosed with psychogenic nonepileptic seizures (PNES). METHODS We conducted a retrospective review of patients diagnosed with PNES in a 5-year period. RESULTS Fifty patients with PNES were identified, giving an estimated incidence of 0.91/100,000 per annum. Thirty-eight were included for review, 15 of whom were male (39%). Eighteen patients had been diagnosed with epilepsy as well as PNES (47%). We demonstrated a gender difference in our patients, with males having higher seizure frequencies, more antiepileptic drug use, and a longer interval before diagnosis of PNES. Females were diagnosed with other conversion disorders more often than males. Impaired social function was observed in PNES, as was resistance to psychological interventions with a subsequent poor response to treatments. CONCLUSIONS PNES remains a difficult condition to treat, and may affect males in proportions higher than those described in previous studies.

Basolateral K+ channel involvement in forskolin‐activated chloride secretion in human colon

1 In this study we investigated the role of basolateral potassium transport in maintaining cAMP‐activated chloride secretion in human colonic epithelium. 2 Ion transport was quantified in isolated human colonic epithelium using the short‐circuit current technique. Basolateral potassium transport was studied using nystatin permeabilization. Intracellular calcium measurements were obtained from isolated human colonic crypts using fura‐2 spectrofluorescence imaging. 3 In intact isolated colonic strips, forskolin and prostaglandin E2 (PGE2) activated an inward transmembrane current (ISC) consistent with anion secretion (for forskolin ΔISC= 63.8 ± 6.2 μA cm−2, n= 6; for PGE2ΔISC= 34.3 ± 5.2 μA cm−2, n= 6). This current was inhibited in chloride‐free Krebs solution or by inhibiting basolateral chloride uptake with bumetanide and 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid DIDS). 4 The forskolin‐ and PGE2‐induced chloride secretion was inhibited by basolateral exposure to barium (5 mM), tetrapentylammonium (10 μM) and tetraethylammonium (10 mM). 5 The transepithelial current produced under an apical to serosal K+ gradient in nystatin‐perforated colon is generated at the basolateral membrane by K+ transport. Forskolin failed to activate this current under conditions of high or low calcium and failed to increase the levels of intracellular calcium in isolated crypts 6 In conclusion, we propose that potassium recycling through basolateral K+ channels is essential for cAMP‐activated chloride secretion.

The opinion of the general practitioner toward clinical management of patients with psychogenic nonepileptic seizures

OBJECTIVE The purpose of this work was to assess the opinion of general practitioners (GPs) regarding the diagnosis of psychogenic nonepileptic seizures (PNES) and the role they feel they should play in the management of the disorder. METHODS Patients with PNES were identified from hospital records. Seizure and patient characteristics were recorded. Their GPs were surveyed regarding their understanding of the diagnosis and ongoing management of PNES. RESULTS Twenty-three patients were identified over a 3-year period as having been diagnosed with PNES. Sixty-five percent of GPs agreed with the diagnosis, and when asked to grade their understanding of the diagnosis (poor = 1, excellent = 10), the mean score was 5.7 (+/-SD 2.3). Thirty-five percent of GPs felt psychological input was of benefit to their patients. Fifty-two percent of GPs felt comfortable following up these patients, either with or without neurology outpatient services. CONCLUSIONS PNES remains a difficult disease to manage. There is a high level of uncertainty regarding the optimum management of PNES among primary care physicians, for which further education is needed.

A study of idiopathic generalised epilepsy in an Irish population.

UNLABELLED Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on clinical and EEG features. PURPOSE The aim of this study was to characterise all cases of IGE with supportive EEG abnormalities in terms of gender differences, seizure types reported, IGE syndromes, family history of epilepsy and EEG findings. We also calculated the limited duration prevalence of IGE in our cohort. METHODS Data on abnormal EEGs were collected retrospectively from two EEG databases at two tertiary referral centres for neurology. Clinical information was obtained from EEG request forms, standardised EEG questionnaires and medical notes of patients. RESULTS two hundred twenty-three patients met our inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic seizures were the most common seizure type reported, 162 (72.65%) having a generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA) was the most common syndrome in our cohort being present in 94 patients (34 male, 60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG studies in all patients showed generalised epileptiform activity. CONCLUSIONS More women than men were diagnosed with generalised epilepsy. Tonic clonic seizures were the most common seizure type reported. EGTCSA was the most frequent syndrome seen. Gender differences were evident for JAE and JME as previously reported and for EGTCSA, which was not reported to date, and reached statistical significance for EGTCA and JME.

Hashimoto's encephalopathy presenting with psychosis and generalized absence status

Sirs: A 61 year old female with a one year history of Hashimoto’s thyroiditis was admitted through the Accident and Emergency Dept. with psychotic symptoms for five days. She had been seen directing traffic outside of her home, talking to deceased relatives and was also reported to have had fluctuating levels of consciousness. She had no previous psychiatric history, but significantly, a family member reported that she had been poorly compliant with L-thyroxine therapy. On examination, she was dishevelled in appearance and noted to be experiencing visual and auditory hallucinations. She was also remarkable for intermittent periods of unresponsiveness, during which flickering movements of her eyelids, and long pauses in speech were apparent, consistent with a diagnosis of generalized absence status. Physical examination revealed no other features of a hypothyroid state. Falstein’s Mini Mental Test Score was 22/30, with deficits mainly in orientation. Laboratory examinations revealed a raised TSH of 16.95 and a normal free T4 level. Antimicrosomal antibodies were positive at a dilute titre of 1:6400. CSF examination and MRI of brain were unremarkable. EEG revealed frequent generalized sharp and slow wave discharge, on a background of fast activity (Fig. 1), consistent with a non convulsive status epilepticus. On review by both neurological and psychiatric services, it was felt that the patient had an organic psychosis and non convulsive status epilepticus, on a background of autoimmune thyroid disease. The patient was treated with anti-convulsants, L-thyroxine and intravenous hydrocortisone. Steroid therapy was discontinued after 6 days and the EEG was repeated at this point. This demonstrated resolution of generalized absence status (Fig. 2). However, the patient’s mental state LETTER TO THE EDITORS

Rapid activation of basolateral potassium transport in human colon by oestradiol

We investigated the effect of oestradiol on basolateral potassium channels in human colonic epithelium. Ion transport was quantified using short circuit current (Isc) measurements of samples mounted in Ussing chambers. Serosal K transport was studied using nystatin permeabilization of the apical membrane. Intracellular pH changes were quantified using spectroflouresence techniques. Experiments were performed with either 10 nM or 1 μM Ca2+ in the apical bathing solution. With 10 nM Ca2+ in the apical bathing solution addition of oestradiol (1 nM) to the basolateral bath produced a rapid increase in current (ΔIK=11.2±1.2 μA.cm−2, n=6). This response was prevented by treatment of the serosal membrane with tolbutamide (1 μM). With 1 μM Ca2+ in the apical bathing solution addition of oestradiol produced a rapid fall in current (ΔIK=−12.8±1.4μA.cm−2), this response was prevented by treatment of the basolateral membrane with tetra‐pentyl‐ammonium (TPeA). These responses were rapid and occurred independently of protein synthesis. Inhibition of basolateral Na+/H+ exchange with either amiloride or a low sodium bathing solution prevented this response. These responses were prevented by inhibition of protein kinase C (PKC) with bis‐indolyl‐maleimide. Oestradiol (1 nM) produced a rapid intracellular alkanization (mean increase=0.11 pH units; n=6; P<0.01). These results suggest that oestradiol rapidly modulates serosal K transport in human colon. These effects depend upon intact Na+/H+ exchange and protein kinase C. We propose a non‐classical, possibly membrane linked, mechanism for oestradiol action in human colonic epithelium.

Acquisition and expression of proximal and distal upper limb stimulus–response curves to transcranial magnetic stimulation

Motor cortex stimulus–response (S/R) curves are an indication of cortical excitability and are of relevance to topographical mapping. The aims of this study were to compare two different methods of collecting data to construct a S/R curve for transcranial magnetic stimulation (TMS) in the upper limbs, to identify reliable summary statistics for the S/R curve, and to determine whether S/R curves predicted motor threshold. Motor evoked potentials (MEP) were obtained from biceps brachii (BB) and abductor pollicis brevis (APB) muscles at rest with a circular coil centered at the vertex. Motor threshold was determined using a validated protocol. MEPs were obtained with 1% increments in intensity or from the average of five trials at 5% increments. The S/R relationships were fitted to linear, S‐shaped, and Boltzmann functions. A linear function determined from the average of five trials accurately summarized our data (r2 from 0.6 to 0.9, P < 0.05, n = 8, for right APB and from 0.6 to 0.9, P < 0.05, n = 8 for right BB). The X‐axis intercept of the line determined using these methods fell between the upper and lower limits of motor threshold in all eight subjects. We propose that MEP values obtained at intervals of 5% averaged over five trials, fitted to a linear function provides a practical means of assessing the S/R characteristics of TMS for proximal and distal upper limb muscles.

Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment

Background We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them. Methods We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008. We reviewed their referral cards and medical records for patient demographics, information on procedures, symptoms, as well as clinical and neurophysiological findings. Results Thirty patients (45.4%) had neuropathies remote from procedural sites and 36 patients (54.5%) had neuropathies in close proximity to procedural sites. Half of the remote neuropathies (15/30) developed following relatively short procedures. In 27% of cases (8/30) remote neuropathies were bilateral. Seven patients developed neuropathies remote from operative sites following hip arthroplasties (7/30: 23.3%), making hip arthroplasty the most common procedure associated with remote neuropathies. Sciatic neuropathies due to hip arthroplasty (12/36, 33.3%) accounted for the majority of neuropathies occurring in close proximity to operative sites. Five medial cutaneous nerve of forearm neuropathies occurred following arterio-venous fistula (AVF) formation. Conclusions An array of surgical procedures may be complicated by neuropathy. Almost half of post-procedure neuropathies occur remote from the site of procedure, emphasizing the need to try to prevent not just local, but also remote neuropathies. Mechanical factors and patient positioning should be considered in the prevention of post-operative neuropathies. There is a possible association between AVF formation and medial cutaneous nerve of forearm neuropathy, which requires further study for validation.

Simultaneous transverse myelitis and acute motor axonal neuropathy in an adult.

Transverse myelitis (TM), which is characterised by focal spinal-cord inflammation, may be idiopathic, parainfectious or disease associated. Diseases associated with TM include demyelinating conditions and connective tissue disorders. Apart from TM due to direct spinal-cord infection, TM is autoimmune.1 Acute motor axonal neuropathy (AMAN), a subtype of Guillain–Barre syndrome (GBS), is characterised by peripheral motor axonal neuropathy, is autoimmune and usually post-infectious. To our knowledge, there are no adult reports of simultaneous TM and AMAN. We report a case of concomitant TM and AMAN in an adult and describe the response to immune modulation. A 19-year-old male presented to the neurology services with a 2-day history of progressive bilateral lower limb weakness, urinary retention and a band of numbness around the waist extending into the feet. Two weeks previously, he had a diarrhoeal illness lasting 3 days. Muscle strength testing revealed weakness of right hip flexion (MRC grade 4), bilateral knee flexion (grade 3), …