Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

https://bic.berkeley.edu/sites/default/files/Rossi_09_TMS%20safety%20review.pdf

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research

Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

The basal ganglia: focused selection and inhibition of competing motor programs.

This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor (tremor during target-directed movements). Additional data from a medical history and the results of a neurologic examination can be combined into one of the following clinical syndromes defined in this statement: enhanced physiologic tremor, classical essential tremor (ET), primary orthostatic tremor, task- and position-specific tremors, dystonic tremor, tremor in Parkinson's disease (PD), cerebellar tremor, Holmes' tremor, palatal tremor, drug-induced and toxic tremor, tremor in peripheral neuropathies, or psychogenic tremor. Conditions such as asterixis, epilepsia partialis continua, clonus, and rhythmic myoclonus can be misinterpreted as tremor. The features distinguishing these conditions from tremor are described. Controversial issues are outlined in a comment section for each item and thus reflect the open questions that at present cannot be answered on a scientific basis. We hope that this statement provides a basis for better communication among clinicians working in the field and stimulates tremor research.

Consensus statement of the Movement Disorder Society on tremor

OBJECTIVE Vitamin B 12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients. METHODS Clinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients before and after treatment. RESULTS The most prominent clinical and electrophysiological findings in all patients were dysfunctions of the posterior column. Corresponding hyperintense lesions in the posterior column of the spinal cord were found in two patients by T2 weighted MRI. Damage to the central motor pathway was identified in four patients. Demyelinating neuropathy was present in one patient and axonal neuropathy in four. All patients showed improvement of their symptoms after treatment with cobalamin. Abnormalities of the spinal cord on MRI disappeared early in recovery. Motor evoked potentials and median somatosensory evoked potentials typically normalised after treatment, whereas tibial somatosensory evoked potentials remained abnormal in most patients. CONCLUSIONS Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B 12 deficiency are diverse. Thus vitamin B 12 deficiency should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.

https://jnnp.bmj.com/content/jnnp/65/6/822.full.pdf

Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)04044-7.pdf

Tremor-correlated cortical activity in essential tremor.

Postural instability is one of the most incapacitating factors in Parkinson’s disease (PD). The underlying deficits and the effects of treatment are still not well understood. The aims of the present study were: (i) to identify abnormalities of postural control in PD patients during unperturbed stance and externally perturbed stance (anterior–posterior tilts of the support surface and of the visual scene); (ii) to assess the effects of l‐dopa medication and subthalamic nucleus (STN) stimulation on posture control; and (iii) to characterize potential differential or additive effects of both treatments. Eight PD patients under chronic STN stimulation were investigated and compared with 10 normal controls. The assessment was performed in a crossover design (± STN stimulation, ± l‐dopa). During unperturbed stance, we recorded measures of spontaneous sway in terms of displacement, velocity and frequency of the centre of pressure (COP), lower body (LB) and upper body (UB) excursions. In addition, inter‐segmental UB–LB coupling was investigated as a measure of axial stiffness. All these measures were abnormally large in patients OFF treatment. Under l‐dopa treatment, the velocity, frequency and coupling measures were reduced, whereas sway amplitude increased. Very similar effects were obtained under STN stimulation, and these effects became more pronounced in the combined treatment condition. In these data, reduction of inter‐segmental coupling correlated with increase in sway amplitude. The finding suggests that axial stiffness reduction under treatment revealed a treatment‐ resistant deficit in the sensorimotor postural control loop. However, these two effects did not correlate with the motor subscores of the unified Parkinson’s disease rating scale (UPDRS), which indicates that they are of minor functional relevance for posture control. A frequency peak in the COP excursions at 0.7–1.1 Hz, which we take to indicate a resonance behaviour of the postural control loop, became reduced under therapy. The reduction of this peak did correlate with most improvements in the UPDRS under therapy. Support surface tilt revealed that an UB righting on the LB segment, which is present in normal controls, is missing in the patients. The postural responses to visual tilt were abnormally large in patients, independent of whether the support was stable or slightly moving, while the control subjects clearly profited from a stable support. This finding suggests that PD patients lack the ability of normal subjects to use sensory or cognitive information when suppressing the destabilizing effect of visual tilt. These abnormal tilt reactions of the patients were resistant to treatment with l‐dopa, STN stimulation and a combination of the two. Overall, the effects of STN stimulation on posture control essentially paralleled those of l‐dopa during both unperturbed and externally perturbed stance.

/pdf/effect-of-chronic-bilateral-subthalamic-nucleus-stn-2altn1re1k.pdf

Effect of chronic bilateral subthalamic nucleus (STN) stimulation on postural control in Parkinson’s disease

Pathological tremors exhibit a nonlinear oscillation that is not strictly periodic. We investigate whether the deviation from periodicity is due to nonlinear deterministic chaotic dynamics or due to nonlinear stochastic dynamics. To do so, we apply various methods from linear and nonlinear time series analysis to tremor time series. The results of the different methods suggest that the considered types of pathological tremors represent nonlinear stochastic second order processes. Finally, we evaluate whether two earlier proposed features capturing nonlinear effects in the time series allow for a discrimination between two pathological forms of tremor for a much larger sample of time series than previously investigated.

Pathological tremors: Deterministic chaos or nonlinear stochastic oscillators?

Several lines of evidence suggest that low-rate repetitive transcranial magnetic stimulation (rTMS) of the motor cortex at 1 Hz reduces the excitability of the motor cortex and produces metabolic changes under and at a distance from the stimulated side. Therefore, it has been suggested that rTMS may have beneficial effects on motor performance in patients with movement disorders. However, it is still unknown in what way these effects can be produced. The aim of the present study is to investigate whether rTMS of the motor cortex (15 min at 1 Hz) is able to modify the voluntary movement related cortical activity, as reflected in the Beretischaftspotential (BP), and if these changes are functionally relevant for the final motor performance. The cortical movement-related activity in a typical BP paradigm of five healthy volunteers has been recorded using 61 scalp electrodes, while subjects performed self-paced right thumb oppositions every 8-20 s. After a basal recording, the BP was recorded in three different conditions, counterbalanced across subjects: after rTMS stimulation of the left primary motor area (M1) (15 min, 1 Hz, 10% above motor threshold), after 15 min of sham rTMS stimulation and following 15 min of voluntary movements performed with spatio-temporal characteristics similar to those induced by TMS. The tapping test was used to assess motor performance before and after each condition. Only movement-related trials with similar electromyographic (onset from muscular 'silence') and accelerometric patterns (same initial direction and similar amplitudes) were selected for computing BP waveforms. TMS- evoked and self-paced thumb movements had the same directional accelerometric pattern but different amplitudes. In all subjects, the real rTMS, but neither sham stimulation nor prolonged voluntary movements, produced a significant amplitude decrement of the negative slope of the BP; there was also a shortening of the BP onset time in four subjects. The effect was topographically restricted to cortical areas which were active in the basal condition, irrespective of the basal degree of activation at every single electrode. No changes in the tapping test occurred. These findings suggest that rTMS of the motor cortex at 1 Hz may interfere with the movement related brain activity, probably through influence on cortical inhibitory networks.

/pdf/effects-of-repetitive-transcranial-magnetic-stimulation-on-3bd0yaltts.pdf

C. H. Lücking

Papers

Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings

Tremor-correlated cortical activity in essential tremor.

Effect of chronic bilateral subthalamic nucleus (STN) stimulation on postural control in Parkinson’s disease

Pathological tremors: Deterministic chaos or nonlinear stochastic oscillators?

Effects of Repetitive Transcranial Magnetic Stimulation on Movement-related Cortical Activity in Humans