Dopaminergic deficit in amyotrophic lateral sclerosis assessed with [I-123] IPT single photon emission computed tomography

Dopamine transporter imaging was performed in 18 patientswith sporadic amyotrophic lateral sclerosis (ALS) and 11 age matched controls with [I-123] IPT(N-(3-iodopropen-2-yl)-2β-carbomethoxy-3β(4-chlorophenyl)-tropane), a new cocaine analogue that selectively binds to the dopamine transporter located on dopaminergic nerve terminals. Image analysis showed that striatal IPT binding was moderately but significantly reduced in the ALS group compared with controls (p<0.01). The reduction of IPT binding was similar for patients with bulbar onsetcompared with those with limb onset. There was no correlation betweenvalues for uptake of striatal IPT and the age of the patients or theduration of the disease. These data indicate that nigrostriatal dopaminergic neurons are subclinically affected in a subset of patientswith sporadic ALS.

     

Spontaneous electromyographic activity of the tongue in amyotrophic lateral sclerosis

Introduction: Detection of denervation in muscles in the craniobulbar area is important to assure widespread lower motor neuron involvement in the diagnosis of amyotrophic lateral sclerosis (ALS). The value of spontaneous activity analysis in needle electromyography (EMG) of the tongue has been questioned in the recent literature. Methods: Spontaneous activity in the tongue and sternocleidomastoid (SCM) muscles was reviewed retrospectively in 17 ALS patients. Results: Needle EMG showed spontaneous activity in the tongue in 14 of 17 patients (82%) and in 6 patients of 17 (35%) in SCM. Spontaneous EMG activity in the tongue was found in patients with and without bulbar symptoms. Conclusions: Needle EMG is a valuable method for assessing clinical and subclinical involvement of the tongue in patients with bulbar and limb onset ALS. Adequate relaxation of the tongue is a prerequisite for proper spontaneous activity recording. Muscle Nerve, 48: 296–298, 2013     

Regional changes in hippocampal T2 relaxation and volume: a quantitative magnetic resonance imaging study of hippocampal sclerosis

OBJECTIVE—The principal MRI features of hippocampal sclerosis are volume loss and increased T2 weighted signal intensity. Minor and localised abnormalities may be overlooked without careful quantitation. Hippocampal T2 relaxation time (HT2) can be quantified, but previously has only been measured on a few thick coronal slices with interslice gaps. In this study HT2 was measured along the entire length of the hippocampus on contiguous slices and used, with quantitative measures of hippocampal volume (HV) and distribution of atrophy, to better define the range of hippocampal sclerosis.
METHODS—Thirty patients with temporal lobe epilepsy, 10 patients with extratemporal localisation related epilepsy and extratemporal lesions, and 20 control subjects were studied using MRI T2 relaxometry and volumetry.
RESULTS—In controls and patients, HT2 was higher in the anterior than the posterior hippocampus. Using HV, morphometric, and HT2 data, patients with temporal lobe epilepsy were classified as unilateral diffuse hippocampal sclerosis (n=16), unilateral focal (n=6), bilaterally affected (n=6), and normal (n=2). In patients with unilateral hippocampal sclerosis, the anterior hippocampus was always affected. In three patients with normal HV, HT2 measurements disclosed unilateral focal abnormalities that corresponded to the EEG lateralisation of epileptic activity. Patients with bilateral hippocampal involvement had an earlier onset of epilepsy than patients with unilateral hippocampal sclerosis.
CONCLUSIONS—Measurement of regional abnormalities of HT2 along the length of the hippocampus provides further refinement to the MRI assessment of the hippocampi in patients with temporal lobe epilepsy and is complementary to volumetric and morphological data.

     

Transitional progressive multiple sclerosis: a clinical and imaging study

OBJECTIVE—To study the prevalence and the naturalcourse of transitional progressive multiple sclerosis (TPMS). Thisclinical form is defined by a progressive course beginning many yearsafter an isolated bout.
METHODS—214 consecutive outpatients with definiteor probable multiple sclerosis were studied. The prevalence of TPMS wasestablished. Patients with TPMS were compared with patients with otherprogressive forms of multiple sclerosis according to the clinicalcourse. A prospective one year follow up study was performed in asubgroup of patients to compare progression of the disease usingclinical indices and MRI.
RESULTS—In this clinical population of 214 outpatients with multiple sclerosis, 55 had secondary progressivemultiple sclerosis (SPMS), 38 primary progressive multiple sclerosis(PPMS), and 12 TPMS. Retrospective analysis of the clinical data ofthese patients shows that TPMS is very similar to SPMS at the beginningof the disease (age at onset, time before progression, clinicalsymptoms at onset, progression index). In addition a cohort of patients was prospectively followed up clinically and by MRI for one year.
CONCLUSIONS—The results did not show anysignificant differences between the three forms during this follow up.However, all data showed a concordant trend suggesting that at thisprogressive stage, TPMS is closer to PPMS in terms of progression ofdisability and new MRI lesions.

     

The EAAT2 (GLT-1) gene in motor neuron disease: absence of mutations in amyotrophic lateral sclerosis and a point mutation in patients with hereditary spastic paraplegia

OBJECTIVES—To investigate if sequence alterationsof the excitatory amino acid transporter gene EAAT2 (GLT-1) may be acontributory factor to the pathogenesis of motor system degeneration.EAAT2 serves as a candidate gene as its reduced expression was reportedin patients with amyotrophic lateral sclerosis (ALS). Furthermore, neurolathyrism, a motor neuron disease clinically related to hereditary spastic paraplegia (HSP), has been associated with an exogenous excitotoxin.
METHODS—Sequence alterations were screened for inthe coding region of EAAT2 in 55 patients with ALS and one family withautosomal dominant HSP (AD-HSP).
RESULTS—In ALS, no sequence alteration in theEAAT2 gene have been found. Interestingly, a heterozygous A79G mutationof the EAAT2 gene was detected in two of seven affected patients withAD-HSP in the same kindred. The absence of cosegregation with thefamilial disease showed that the detected variant was not the cause of disease. The A79G sequence variant was not found in 55 patients withALS or in 50 non-neurological controls.
CONCLUSION—The allelic variant of the EAAT2 genein conjunction with the primary gene defect may be a modifying factorfor the highly variable AD-HSP phenotype.

     

Overactivity of cervical premotor neurons in Parkinson's disease

OBJECTIVES—Cortical command to upper limb motorneurons is transmitted, in humans, not only through the monosynapticcorticomotor neuronal pathway, but also through cervical premotorneurons. Whether activity in this non-monosynaptic corticospinalpathway is modified in Parkinson's disease was explored.
METHODS—Ongoing EMG activity recorded in wristextensors during tonic extension of the wrist is suppressed by a volleyevoked by stimulating the superficial radial nerve. It has been shownthat this cutaneous induced suppression is due to inhibition oftransmission of the cortical command at a premotor neuronal level. Bycomparing the cutaneous induced EMG depression between 45 de novoparkinsonian patients and 23 age matched controls it has been possibleto appreciate if and to what extent the "non-monosynaptic" part ofthe cortical command is modified in these patients.
RESULTS—At the early stage of the illness the EMGdepression, reflecting the "non-monosynaptic" part of the corticalcommand, was bilaterally increased despite very asymmetric clinicalstatus. When the duration of the disease was more than 36 months, EMG depression returned to its control level. No correlation was found between the amount of the EMG depression and parkinsonian symptoms before and after levodopa treatment.
CONCLUSION—Increase of the relative"non-monosynaptic" part of the cortical command could reflect acompensatory motor mechanism elaborated upstream from the motorcortex

     

Clinical utility of trapezius muscle studies in the evaluation of amyotrophic lateral sclerosis.

Needle electromyography (EMG) and determining the motor evoked potential (MEP) of the genioglossus (tongue) are difficult to perform in evaluation of the craniobulbar region in patients with amyotrophic lateral sclerosis (ALS). Needle EMG and MEP determination in the upper trapezius were carried out in 17 consecutive ALS patients. The needle EMG parameters recorded included abnormal spontaneous activity and motor unit action potential morphology. An upper motor neuron lesion was presumed when either response to cortical stimulation was absent, or the central conduction time was delayed (>mean + 2 SD). Of the 12 patients with limb-onset ALS, using needle EMG, 11 were found to have abnormalities in the upper trapezius, and only five in the tongue. Three of the six patients with isolated limb involvement had abnormal MEP findings. In conclusion, electrophysiological studies of the upper trapezius are useful in ALS patients without bulbar symptoms.     

Altered antibody pattern to Epstein-Barr virus but not to other herpesviruses in multiple sclerosis: a population based case-control study from western Norway

OBJECTIVE—The prevalence of anti-EBV antibodieswas studied in a group of 144 patients with multiple sclerosis and 170 age, sex, and area matched controls from the county of Hordaland,western Norway. The prevalence of three other herpesviruses, herpessimplex virus (HSV), varicella zoster virus (VZV), andcytomegalovirus (CMV), were also included.
METHODS—Antibodies to various virus antigens weredetermined by enzyme linked immunosorbent assay (ELISA) and indirectimmunfluorescence (IIF) in serum samples from 144 patients withmultiple sclerosis and 170controls.
RESULTS—All of the 144 patients with multiplesclerosis had IgG antibodies to EBV compared with 162 of 170 controls(p=0.008). The frequency of IgG antibodies to EBV capsid antigen (VCA),nuclear antigen (EBNA), and early antigen (EA) was significantly higher in patients with multiple sclerosis compared with the controls (p<0.000001, p=0.01, and p<0.0001 respectively). The presence ofantibodies was independent of the initial course of the disease and thedisease activity at the time of blood sampling. The prevalence of IgGantibodies to HSV, CMV, and VZV did not differ between cases and controls.
CONCLUSION—The results suggest a role for EBV inthe aetiology of multiple sclerosis.

     

Peripherally induced oromandibular dystonia

OBJECTIVES—Oromandibular dystonia (OMD) is afocal dystonia manifested by involuntary muscle contractions producingrepetitive, patterned mouth, jaw, and tongue movements. Dystonia isusually idiopathic (primary), but in some cases it follows peripheralinjury. Peripherally induced cervical and limb dystonia is wellrecognised, and the aim of this study was to characterise peripherallyinduced OMD.
METHODS—The following inclusion criteria were usedfor peripherally induced OMD: (1) the onset of the dystonia was withina few days or months (up to 1 year) after the injury; (2) the traumawas well documented by the patient's history or a review of their medical and dental records; and (3) the onset of dystonia was anatomically related to the site of injury (facial and oral).
RESULTS—Twenty seven patients wereidentified in the database with OMD, temporally and anatomicallyrelated to prior injury or surgery. No additional precipitant otherthan trauma could be detected. None of the patients had any litigationpending. The mean age at onset was 50.11 (SD 14.15) (range 23-74)years and there was a 2:1 female preponderance. Mean latency betweenthe initial trauma and the onset of OMD was 65 days (range 1 day-1year). Ten (37%) patients had some evidence of predisposing factorssuch as family history of movement disorders, prior exposure toneuroleptic drugs, and associated dystonia affecting other regions oressential tremor. When compared with 21 patients with primary OMD,there was no difference for age at onset, female preponderance, andphenomenology. The frequency of dystonic writer's cramp, spasmodicdysphonia, bruxism, essential tremor, and family history of movementdisorder, however, was lower in the post-traumatic group (p<0.05). Inboth groups the response to botulinum toxin treatment was superior tomedical therapy (p<0.005). Surgical intervention fortemporomandibular disorders was more frequent in the post-traumaticgroup and was associated with worsening of dystonia.
CONCLUSION—The study indicates thatoromandibular-facial trauma, including dental procedures, mayprecipitate the onset of OMD, especially in predisposed people. Promptrecognition and treatment may prevent further complications.

     

Clinical study of primary progressive multiple sclerosis in Northern Ireland, UK

OBJECTIVE—To investigate the clinical anddemographic characteristics of primary progressive multiple sclerosis(PPMS) in Northern Ireland and to establish a database of such patientsfor genetic and immunological studies and future therapeutic trials.
METHODS—Diagnosis and categorisation wereperformed by two neurologists, potential cases being identified fromthe following sources: neurology outpatient clinics; neurologyinpatients; a review of hospital discharges; and an ongoingepidemiological study of multiple sclerosis in Northern Ireland. Onlythose with a progressive course from onset and a clear history of noprior relapses were accepted. Potential cases were invited forinterview and assessment, the minimal record of disability (MRD) being established.
RESULTS—One hundred and eleven cases of PPMS havebeen identified, 63 women and 48 men (ratio 1.3:1), with a mean age atonset of 39.5 (SD 11.0) (range 17-66)years, and mean disease durationof 13.6 (SD 9.3)years. The mean interval between onset and diagnosis was 4.7 (SD 4.2) years. Nineteen patients (17.1%) did not satisfy therequirements for any category in the Poser criteria. Motor disturbancewas the commonest mode of onset (67.6%) with visual loss occurringonly rarely at onset (3.6%). Kurtzke EDSS scores were concentrated atthe upper end of the scale with a median of 6.0 and levels ofunemployment and financial dependence were high.
CONCLUSIONS—PPMS in Northern Ireland has agenerally later age at onset, lower female preponderance, andpredominantly motor onset compared with other subgroups of multiplesclerosis. The delay to diagnosis reflects the often insidious onsetand the nature of the clinical course makes application of the Posercriteria difficult. Levels of neurological impairment, disability, andhandicap as measured by the MRD are high.

     

Natural history and survival of 14 patients with corticobasal degeneration confirmed at postmortem examination

OBJECTIVE—To analyse the natural history andsurvival of corticobasal degeneration by investigating the clinicalfeatures of 14 cases confirmed by postmortem examination.
METHODS—Patients with definite corticobasaldegeneration were selected from the research and clinical files ofseven tertiary medical centres in Austria, the United Kingdom, and theUnited States. Clinical features were analysed in detail.
RESULTS—The sample consisted of eight female andsix male patients; mean age at symptom onset was 63 (SD 7.7) years, andmean disease duration was 7.9 (SD 2.6) years. The most commonlyreported symptom at onset included asymmetric limb clumsiness with orwithout rigidity (50%) or tremor (21%). At the first neurologicalvisit, on average 3.0 (SD 1.9) years after symptom onset, the mostoften encountered extrapyramidal features included unilateral limbrigidity (79%) or bradykinesia (71%), postural imbalance (45%), andunilateral limb dystonia (43%). Ideomotor apraxia (64%), and to alesser extent cortical dementia (36%), were the most common cortical signs present at the first visit. During the course of the disease, virtually all patients developed asymmetric or unilateral akinetic rigid parkinsonism and a gait disorder. No patient had a dramatic response to levodopa therapy. Median survival time after onset ofsymptoms was 7.9 (SD 0.7) (range, 2.5-12.5) years, and, after thefirst clinic visit, 4.9 (SD 0.7) (range, 0.8-10) years. Early bilateral bradykinesia, frontal syndrome, or two out of tremor, rigidity, and bradykinesia, predicted a shorter survival.
CONCLUSION—The results confirm thatunilateral parkinsonism unresponsive to levodopa and limb ideomotorapraxia are the clinical hallmarks of corticobasal degeneration, andonly a minority of patients with corticobasal degeneration present withdementia. The study also suggests that a focal cognitive andextrapyramidal motor syndrome is indicative of corticobasaldegeneration. Survival in corticobasal degeneration was shortened bythe early presence of (more) widespread parkinsonian features orfrontal lobe syndrome.

     

Quality of life in multiple sclerosis in France,Germany, and the United Kingdom

OBJECTIVE—To assess the quality of life (QoL) of patients with multiple sclerosis in France, Germany, and the United Kingdom with a cross sectional study.
METHODS—Patients were classified into three severity groups according to the expanded disability severity scale (EDSS); stage I, II, and III, corresponding to mild (EDSS 1.0-3.5), moderate (EDSS 4.0-6.0), or severe (EDSS 6.5-8.0) multiple sclerosis respectively. Ninety patients with multiple sclerosis and 30 control patients without multiple sclerosis were recruited in each country. Control patients were matched to the patients with multiple sclerosis according to age and sex. Quality of life was assessed using the functional status questionnaire (FSQ).
RESULTS—The aspects of QoL that were mostly affected in the three countries under study were physical function and general wellbeing. Social role function decreased with increased severity of disease in France and in particular in Germany. Multiple sclerosis did not seem to have an impact on psychological function. The QoL of control patients was systematically higher than that of patients with multiple sclerosis.
CONCLUSIONS—Use of such a generic scale showed that progression of multiple sclerosis is accompanied by a decrease in QoL and suggested that this could be a relevant measurement in assessing the effect of treatment and progression of disease. Variation between countries, however, may be important.

     

The prevalence of multiple sclerosis in the Leeds Health Authority

OBJECTIVES—To determine the prevalence of multiplesclerosis in the Leeds Health District.
METHODS—Multiple sources of case ascertainmentwere used—namely, neurology departments, hospital episode statistics,general practitioners, the Leeds branch of the Multiple SclerosisSociety, the West Yorkshire Multiple Sclerosis Therapy Centre,community physiotherapists and occupational therapists, the LeedsWheelchair Centre, and the Young Disabled Unit. Data collection wasfrom retrospective analysis of hospital and primary care case records.A population based incidence register was established by prospectivelyregistering all new patients with diagnoses of multiple sclerosis.
RESULTS—On prevalence day, 30 April 1996, 712 people with multiple sclerosis were identified living in Leeds(population 732 061), giving a prevalence of 97/10⁵. Theprevalence for definite and probable multiple sclerosis was84/10⁵, and for suspected multiple sclerosis it was13/10⁵. The sex ratio of prevalent people with multiplesclerosis was 2.79 to 1 women to men. The mean age of prevalent caseswas 51years, the mean age at symptom onset was 34 years, and the mean duration of disease was 16 years. Forty cases were prospectively reported as incident cases from 1 November 1995 to 1 February 1996.
CONCLUSIONS—The prevalence of multiple sclerosisin Leeds was found to be similar to that in the south of the UnitedKingdom but lower than that in Scotland. There is no evidence of alatitudinal gradient of increasing prevalence of multiple sclerosisfrom the south to the north of England.

     

Differences in duration of Huntington's disease based on age at onset

OBJECTIVES—Data from asample of 2494 patients affected with Huntington's disease (HD),collected as part of the National Research Roster for HuntingtonDisease Patients and Families, were examined to determine if there wasa relation between age at onset and duration of illness.
METHODS—Sufficientdata for inclusion in analysis was available from 2068 patients, ofwhom 828 were deceased and 1240 were living. The median duration ofdisease was 21.4 years with a range of 1.2 to 40.8 years. Patients werecategorised into one of four groups based on their age at onset.
RESULTS—Significantdifferences in duration based on the age at onset were found(p<0.025), with juvenile and late onset patients with HD havingshorter duration of illness compared with those with an onset between20-49 years.
CONCLUSIONS—Durationof disease is influenced by the age at symptom onset with juvenile andlate onset patients having the shortest duration.

     

Awaji ALS criteria increase the diagnostic sensitivity in patients with bulbar onset

ObjectiveTo assess whether Awaji criteria improve the sensitivity of diagnosis for amyotrophic lateral sclerosis (ALS). In Awaji ALS criteria, fasciculation potentials are regarded as evidence of acute denervation in the presence of chronic neurogenic changes on needle electromyography.MethodsWe reviewed clinical and neurophysiological data of 113 consecutive patients who were suspected as suffering ALS. The six muscles (trapezius, biceps, first dorsal interosseous, T10-paraspinalis, vastus lateralis, and tibialis anterior muscles) were examined by EMG, focusing on the presence of fasciculation potentials. The sensitivity of revised El Escorial (R-EEC) and Awaji criteria was compared.ResultsProbable or definite ALS was diagnosed in 61% of the patients by R-EEC and 71% by Awaji criteria. By applying Awaji criteria; (1) 17 of the 44 patients categorized as possible ALS by R-EEC reached to probable/definite ALS, 11 of whom had bulbar onset, (2) in 48 patients with bulbar onset, the proportion of probable/definite ALS increased from 59% to 82%, (3) in 62 patients with limb onset, the proportion of probable/definite ALS was 61% (63% by R-EEC).ConclusionsAwaji criteria improve the sensitivity of ALS diagnosis in patients with bulbar onset, but not in those with limb onset.SignificanceAccepting fasciculation potentials as evidence of acute denervation increases the diagnostic sensitivity of ALS, particularly in patients with bulbar onset, and contributes to early diagnosis.     

Muscle‐specific kinase antibodies: A novel cause of peripheral nerve hyperexcitability?

Introduction: Antibodies that target the postsynaptic neuromuscular junction (NMJ) protein, muscle‐specific kinase (MuSK), have been associated with myasthenia gravis (MG), often with cramps and fasciculations, after administration of acetylcholinesterase inhibitors (AChE‐I). Methods: In this report, 2 patients are described with elevated MuSK antibodies and evidence of peripheral nerve hyperexcitability (PNH) unrelated to AChE‐I medication. Results: Patient 1 presented with facial neuromyotonia and fasciculations, without overt weakness. EMG studies demonstrated myokymic discharges in facial muscles, with bursts of discharges after voluntary activation, and widespread fasciculation potentials in limb muscles. Patient 2 presented with bulbar weakness and fasciculations in the tongue and limbs, initially diagnosed as bulbar‐onset amyotrophic lateral sclerosis. Subsequent investigation identified the presence of MuSK antibodies. Conclusions: We hypothesize that MuSK antibodies may induce these phenotypes through disruptive actions at the NMJ, in particular the binding of acetylcholinesterase (AChE) to MuSK via its collagen Q (ColQ) tail, producing a reduction in synaptic AChE activity. Muscle Nerve 48:819–823, 2013     

Botulinum A toxin as a treatment of detrusor- sphincter dyssynergia in patients with spinal cord injury: MRI controlled transperineal injections

OBJECTIVES—To correlate clinical and urodynamicfindings with MRI in patients with spinal cord injury anddetrusor-sphincter dyssynergia who were consecutively treated withtransperineal injections of botulinum-A toxin (BTX-A) under EMG control.
METHODS—Six patients with spinal cord injury andupper motor neuron bladder dysfunction associated with detrusor-sphincter dyssynergia were prospectively analysed. One hundredinternational units (IU) BTX-A (Botox® in 1 ml normal saline withoutpreservative) diluted 1 to 1 with 1 ml gadopentetate were injectedtransperineally under EMG control. MRI was started immediately afterneedle withdrawal.
RESULTS—In all six patients gadopentetate waslocated in the external urethral sphincter on MRI. In no patient didtraces of gadopentetate appear in the perineal musculature located inthe vicinity of the external urethral sphincter. No patient developedresistance to BTX-A. All patients showed an (ongoing) improvement oftheir voiding function after BTX-A injections.
CONCLUSIONS—Transperineal injections of BTX-Aunder EMG control are efficient in the release or amelioration of lowerurinary tract obstruction due to detrusor sphincter dyssynergia inpatients with spinal cord injury. Despite well described methods, EMGof the external urethral sphincter is difficult and it is not possibleto definitively exclude false recordings of the surrounding perinealmusculature. By the use of MRI it was shown that both the EMGrecordings and transperineal injection method are precise.

     

Physiological effects of selective tibial neurotomy on lower limb spasticity

OBJECTIVES—To assess by electrophysiology theeffect of tibial selective neurotomy on muscle imbalance of the spastic ankle.
METHOD—The amplitudes of the H reflexes, Mresponses (muscle contractions recorded after stimulation of the tibialnerve), and Hmax:Mmax ratio were recorded in 12 patients with chroniclower limb spasticity, before and one month after tibial selectiveneurotomy. Recordings were done on medial and lateral gastrocnemius andsoleus muscles.
Clinical evaluation was done with both global (Held's score)and analytical tests (step measurements, gait velocity, and ankleangulation during active and passive movements).
RESULTS—After neurotomy, gait improved in allpatients. Held 's score of spasticity was better in all patients.Active dorsiflexion of the ankle was unchanged in three patients, butthe others improved by 5° to 12°. Hmax, Mmax, and Hmax:Mmax ratioswere lower. The Hmax on the gastrocnemius muscle, clinical strength,Mmax of all the muscles, and Hmax:Mmax ratio for the soleus and lateralgastrocnemius muscle were significantly lower after surgery.
CONCLUSION—There was an improvement of clinicaland electrophysiological spastic indices after selective tibialneurotomy. Neurotomy acted not only on motor neurons by decreasingstrength, but also the reflex enlargement by decreasing sensory afferents.

     

Effects of antipsychotic medication on electromyographic responses to transcranial magnetic stimulation of the motor cortex in schizophrenia

OBJECTIVE—To assess the effect ofantidopaminergic antipsychotic medication on the electromyographic(EMG) responses of thenar muscles to transcranial magnetic stimulation(TMS) of the motor cortex in schizophrenic patients.
METHODS—A group of nine drug naïveschizophrenic patients was compared with a group of nine schizophrenicpatients established on neuroleptic medication. Surface EMG recordingswere made from the thenar muscles while patients maintained a weakisometric voluntary contraction. TMS was applied using a 9 cm circularstimulating coil centred over the vertex. The EMG responses to up to 50 magnetic stimuli were rectified and averaged.
RESULTS—There was no difference in threshold TMSstrength for eliciting compound motor evoked potentials (cMEPs), or intheir latency, in drug naïve and medicated patients. In some patientsthe silent period (SP) was clearly made up of two parts and thepercentage of control levels of voluntary EMG was measured in eachcomponent. During the early component of the SP there was a weaker(P<0.05) suppression of EMG in the medicated patients (mean 73.9 (SEM) 5.5% of control levels) compared with the drug naïve patients (54.7 (SEM) 7.3% of control levels). This resulted in the latency of maximumsuppression of voluntary EMG being longer (P<0.05) in the medicatedpatients (38.3 (2.4) ms) than in the drug naïve patients (28.2 (0.7)ms). During the late component of the SP voluntary EMG was reduced tosimilar levels (P>0.05) in both medicated (48.2 (7.7)% of controllevels) and drug naïve (58 (7.8)% of control levels) patients.
CONCLUSION—The results are discussed withreference to the disrupted inhibition seen in the early part of the SPin Parkinson's disease and drug induced parkinsonism. The future usesof motor responses to TMS as a marker for the status of antipsychoticmedication are considered.

     

The effect of unilateral posteroventral pallidotomy on the kinematics of the reach to grasp movement

OBJECTIVE—to assess postoperative effects ofunilateral posteroventral pallidotomy on the organisation of upper limb movement.
METHODS—A three dimensional kinematic system(ELITE, B|T|S| Italy) was used to record reach to grasp movementsto objects of either small (0.7 cm) or large (8 cm) diameter placed ata reaching distance of either 20 or 30 cm. Four patients withParkinson's disease were assessed in "off" (12 hours withoutmedication) and "on" (1 hour after administration of medication)preoperatively and postoperatively.
RESULTS—Duration of the movement and the timespent in arm deceleration were significantly reduced after surgery.However, movement patterning according to object size was adverselyaffected. Postoperatively, all four patients showed an abnormal patternof a longer movement duration, and three showed a longer time ofreaching arm deceleration, for reach to grasp movements to the largeobject than for those to the small object.
CONCLUSION—Posteroventral pallidotomy seems to bebeneficial in reducing bradykinesia of upper limb movements but mayhave "costs" to movement patterning, particularly for reach tograsp movements to objects of differing sizes. This study raisesinteresting questions about the role of the globus pallidus interna incoordinating stimulus bound visual information with appropriate motor patterning.