[Causes of camptocormia]. / Ursachen der Kamptokormie.

In this society with an ever increasing number of the elderly there is an increasing number of causes of a bent spine syndrome (camptocormia/dropped head syndrome). The causes include neurological, neuro-orthopedic, rheumatological and psychiatric disorders. Parkinson's disease, dystonia and neuromuscular diseases (motor neuron disease, myositis and muscular dystrophy) with weakness of the axial muscles may result in bent spine syndrome and is often combined with a dropped head. Disc herniation, hypertrophic spondylosis or pseudospondylolisthesis with spinal narrowing may lead to an abnormal flexion of the trunk. Ankylosing spondylitis can produce a disabling bent spine syndrome. Camptocormia may also be mimicked by osteoporotic fractures of the vertebral bones with wedge-shaped vertebrae. In some cases camptocormia is related to a psychogenic disorder.

[The new S2k AWMF guideline for the treatment of Bell's palsy in commented short form]. / Die neue S2k AWMF Leitlinie zur idiopathischen Fazialisparese in kommentierter Kurzform.

A new S2k AWMF guideline for the treatment of idiopathic facial palsy has been published. An accurate differential diagnosis is indispensable as 25-40% of all facial palsy cases are of non-idiopathic origin. It is explicitly recommended to treat patients with idiopathic facial palsy with steroids. Steroids favour a complete recovery, decrease the risk of synkinesis, autonomic sequelae and contractures. Adjuvant antiviral therapy cannot be recommended. On current data there is not sufficient evidence that the combination of steroids with antiviral drugs has a benefit for the patients. Even when not supported by randomized trials, adjuvant symptomatic therapy to protect the cornea and to avoid complications is recommended. There is no scientific evidence that physical therapy has any benefit but it should be taken into account because of psychological reasons. A benefit of acupuncture has not been proven. If eye closure remains incomplete as result of defective healing, one therapeutic option is lid loading of the upper eye lid. Moreover, in case of severe persistent palsy, several well-established microsurgical nerve and muscle plasty procedures are available.

Changes in interhemispheric inhibition following successful epilepsy surgery: a TMS study.

Epileptic foci can influence cortical excitability, brain perfusion and metabolism not only directly in the focus or perifocally, but also in remote areas. Effects of successful epilepsy surgery on cortical networks and changes in excitability have rarely been addressed. We report a study on changes in interhemispheric inhibition following successful surgical removal of an epileptic focus. Eighteen patients (11 females, 7 males, mean age 34.2 years) were enrolled in this transcranial magnetic stimulation (TMS) study. All patients were seizure free after surgery and had identical antiepileptic medication pre- and postsurgically. Investigations were performed before and at least 3 months after surgery. Motor thresholds (MT) and motor evoked potentials (MEPs) of interhemispheric paired pulse paradigms were investigated on both hemispheres. Resection of the epileptic focus resulted in a significant change in interhemispheric inhibition (IHI). The ability of the non-focal hemisphere to inhibit the motor cortex (M1) of the focal hemisphere significantly increased (p=0.02) and normalized to the level of the other hemisphere. In summary, this TMS study suggests that an epileptic focus can modulate interhemispheric inhibitory interactions between the motor cortices. A decreased susceptibility of M1 of the focal hemisphere or alterations in the non-focal hemispheric inhibitory output may be underlying mechanisms. These findings may contribute to a better understanding of widespread functional impairments in focal epilepsy.

Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial.

Late-onset glycogen storage disease type 2 (GSD2)/Pompe disease is a progressive multi-system disease evoked by a deficiency of lysosomal acid alpha-glucosidase (GAA) activity. GSD2 is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. Since 2006 alglucosidase alfa has been licensed as a treatment in all types of GSD2/Pompe disease. We here present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 44 late-onset GSD2 patients with various stages of disease severity. Alglucosidase alfa was given i.v. at the standard dose of 20 mg/kg every other week. Assessments included serial arm function tests (AFT), Walton Gardner Medwin scale (WGMS), timed 10-m walk tests, four-stair climb tests, modified Gowers' maneuvers, 6-min walk tests, MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels and SF-36 self-reporting questionnaires. All tests were performed at baseline and every 3 months for 12 months of ERT. We found significant changes from baseline in the modified Gowers' test, the CK levels and the 6-min walk test (341 +/- 149.49 m, median 342.25 m at baseline; 393 +/- 156.98 m; median 411.50 m at endpoint; p = 0.026), while all other tests were unchanged. ERT over 12 months revealed minor allergic reactions in 10% of the patients. No serious adverse events occurred. None of the patients died or required de novo ventilation. Our clinical outcome data imply stabilization of neuromuscular deficits over 1 year with mild functional improvement.

The effect of carpal tunnel release on median nerve flattening and nerve conduction.

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and extensive surveys have been given on the time course of electrophysiological findings pre- and postoperatively. In patients with clinical and electrophysiological confirmed diagnosis of CTS surgical decompression of the carpal tunnel is a first line treatment and has proven to be successfull in 70 to 90% of all cases. The objective of this work was to study the morphological changes of the median nerve after endoscopic release of the carpal tunnel. We used high resolution ultrasound to quantify flattening of the median nerve and to calculate a flattening ratio before endoscopic release as well as 2 weeks and 3 months postoperatively. Ten patients with clinical and electrophysiological confirmed CTS were included in the study. There was significant normalization of the calculated flattening ratio of the median nerve already 2 weeks after surgical release, whereas nerve conduction studies needed a longer period of time to normalize and thus were still abnormal 3 months postoperatively. We conclude that ultrasound is a simple and excellent objective method for visualizing the morphological recovery of the median nerve very early after decompression surgery. In complex cases with unsatisfactory outcome ultrasonography may prove useful in confirming successfull or failed decompression of the median nerve.

Low level of intracortical inhibition in children shown by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to evaluate the integrity and maturation of the corticospinal tract. TMS was used in this study to compare intracortical inhibition (ICI) in children, adolescents, and adults. The paired-pulse technique of TMS with interstimulus intervals of 2 ms was used to determine the ratio of conditioned (cMEP) and unconditioned amplitudes (ucMEP) that measures ICI. In experiment 1 (Exp 1) stimulus intensity was adapted to motor threshold (50 healthy subjects; 24 male, 26 female, median age 13.5 years, range 6.3 - 34 years) and in experiment 2 (Exp 2) stimulus intensity was adapted to the ucMEP (200 - 400 microV). Children (quotient of cMEP and ucMEP: Exp. 1: 0.71 +/- 0.41, Exp. 2: 0.82 +/- 0.25) had significantly less ICI compared to adults (Exp. 1: 0.21 +/- 0.19, mean +/- STD, Exp. 2: 0.35 +/- 0.22, in both experiments p < 0.001). Recently, ICI has been linked to the regulating function of GABAergic cortical interneurons on practice-dependent neuronal plasticity. Therefore, the lower ICI in children points to maturation processes that may have implications for the greater capacity of practice-dependent neuronal plasticity in children.

Paraneoplastic cerebellar degeneration and nephrotic syndrome preceding Hodgkin's disease: case report and review of the literature.

A patient presented with symptoms of cerebellar degeneration and nephrotic syndrome. A work-up at that time failed to reveal an underlying disease; however, 20 months later Hodgkin's disease was diagnosed. Hodgkin's lymphadenopathy developed 2 wk after prednisone therapy for the nephrotic syndrome had been discontinued. Systemic polychemotherapy resulted in complete remission of both Hodgkin's disease and nephrotic syndrome, while the neurological deficit persisted. Patients with unexplained cerebellar degeneration and/or nephrotic syndrome demand extensive evaluation for the presence of Hodgkin's disease, and steroid therapy may delay diagnosis.

Inhibitory conditioning stimulus in transcranial magnetic stimulation reduces the number of excited spinal motor neurons.

OBJECTIVE: To study the mechanisms of amplitude attenuation caused by a transcranial magnetic conditioning stimulus. Both conventional MEPs and the recently described triple stimulation technique (TST) were applied; the latter to improve the quantification of the response size decrease. METHODS: TST uses a peripheral collision method to eliminate the effects of desynchronization of the transcranial magnetic stimulation (TMS) induced spinal motor neuron discharges. The attenuation of motor evoked potentials (MEPs) and responses to TST was studied in 10 healthy volunteers using the conditioning-test paradigm with 2 ms interstimulus intervals. RESULTS: Conventional MEPs and responses to TST demonstrated a marked attenuation by the preceding conditioning stimulus in all subjects. The ratio of MEP to TST amplitudes was the same in conditioned and unconditioned responses. CONCLUSIONS: Our findings suggest that the transcranial conditioning stimulus does not change the degrees of desynchronization of spinal motor neuron discharges, but results in a reduced number of excited alpha motor neurons. This reduction can be estimated by both MEPs and TST.

Valproic acid triggers acute rhabdomyolysis in a patient with carnitine palmitoyltransferase type II deficiency.

A 47-year-old man suffering from a bipolar disorder and intermittent myoglobinuria presented with acute rhabdomyolysis with renal failure after starting therapy with valproic acid. On morphological examination, skeletal muscle revealed increased lipid storage. Biochemically, decreased enzyme activity of carnitine palmitoyltransferase (CPT) type II with carnitine levels in the lower limit was found. Genetic analysis detected the common Ser113Leu substitution on one allele of the CPT2 gene. We conclude that valproic acid should be avoided in patients with CPT type II deficiency.

Modulation of upper extremity motor evoked potentials by cutaneous afferents in humans.

The excitability of motoneurons controlling upper limb muscles in humans may vary with cutaneous nerve stimulation. We investigated the effect of noxious and non-noxious conditioning stimuli applied to right and left digit II and right digit V on motor evoked potentials (MEPs) recorded from right thenar eminence, abductor digiti minimi, biceps and triceps brachii muscles in twelve healthy subjects. Transcranial magnetic stimulation (TMS) was applied at interstimulus intervals (ISI) ranging from 40 to 160 ms following conditioning distal digital stimulation. TMS and transcranial electrical stimulation (TES) were compared at ISI 80 ms. Painful digital stimulation caused differential MEP amplitude modulation with an early maximum inhibition in hand muscles and triceps brachii followed by a maximum facilitation in arm muscles. Stimulation of different digits elicited a similar pattern of MEP modulation, which largely paralleled the behavior of cutaneous silent periods in the same muscles. Contralateral digital stimulation was less effective. MEPs following TMS and TES did not differ in their response to noxious digital stimulation. MEP latencies were shortened by cutaneous stimuli. The observed effects were stimulus intensity dependent. We conclude that activation of A-alpha and A-delta fibers gives rise to complex modulatory effects on upper limb motoneuron pools. A-delta fibers initiate a spinal reflex resulting in MEP amplitude reduction in muscles involved in reaching and grasping, and MEP amplitude facilitation in muscles involved in withdrawal. These findings suggest a protective reflex mediated by A-delta fibers that protects the hand from harm. A-alpha fibers induce MEP latency shortening possibly via a transcortical excitatory loop.

Nociceptive fingertip stimulation inhibits synergistic motoneuron pools in the human upper limb.

BACKGROUND: Activation of distinct muscle groups organized in a stereotyped manner ("muscle synergies") is thought to underlie the production of movement by the vertebrate spinal cord. This results in movement with minimum effort and maximum efficiency. The question of how the vertebrate nervous system inhibits ongoing muscle activity is central to the study of the neural control of movement. OBJECTIVE: To investigate the strategy used by the human spinal cord to rapidly inhibit muscle activation in the upper limb. METHODS: The authors performed a series of experiments in 10 healthy subjects to assess the effect of nociceptive cutaneous stimulation on voluntarily contracting upper limb muscles. They recorded the electromyogram (EMG) with surface electrodes placed over various upper limb muscles. RESULTS: The authors found evidence of a simple inhibitory strategy that 1) was dependent on the intensity of the stimulus, 2) was maximally evoked when stimulation was applied to the fingertips, 3) preceded the earliest onset of voluntary muscle relaxation, and 4) produced inhibition of EMG activity in specific upper limb muscle groups. Nociceptive fingertip stimulation preferentially inhibited contraction of synergistic muscles involved in reaching and grasping (intrinsic hand muscles, forearm flexors, triceps) while having little effect on biceps or deltoid. CONCLUSIONS: Neural circuitry within the human spinal cord is organized to inhibit movement by rapidly deactivating muscles that constitute distinct muscle synergies. This strategy of selective and concurrent deactivation of the same basic elements that produce synergistic movement greatly simplifies motor control.

Pain perception during self-reported distress and calmness in patients with borderline personality disorder and self-mutilating behavior.

Self-mutilation occurs in 70-80% of patients who meet DSM-IV criteria for borderline personality disorder. Approximately 60% of these patients report that they do not feel pain during acts of self-mutilation such as cutting or burning. Findings of recent studies measuring pain perception in patients with BPD are difficult to interpret since variables such as distress, dissociation or relevant psychotropic medication have not been controlled. The Cold Pressor Test (CPT) and the Tourniquet Pain Test (TPT) were administered to 12 female patients with BPD who reported analgesia during self-mutilation and 19 age-matched healthy female control subjects. All subjects were free of psychotropic medication. The patients were studied on two occasions: during self-reported calmness and during intensive distress (strong urge to cut or burn themselves). Even during self-reported calmness, patients with BPD showed a significantly reduced perception of pain compared to healthy control subjects in both tests. During distress, pain perception in BPD patients was further significantly reduced as compared with self-reported calmness. The present findings show that self-mutilating patients with BPD who experience analgesia during self-injury show an increased threshold for pain perception even in the absence of distress. This may reflect a state-independent increased pain threshold which is further elevated during stress. Interpretation of these findings is limited by their reliance upon self-reports.

Effects of repetitive transcranial magnetic stimulation on movement-related cortical activity in humans.

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.

Classical conditioning of the electrically elicited blink reflex in humans: a new method of data analysis.

The eyeblink conditioning paradigm is a well-established model to study learning processes in humans and animals. Especially results from animal studies have supplied new insight into physiological pathways and brain structures involved in associative motor learning and memory. An important role of the cerebellum and its afferent fiber systems could be shown. Recent studies in humans have given evidence that results of animal experiments can be applied directly to the human condition. A high variation of baseline EMG activity and/or spontaneous blinks may influence the analysis of classical conditioning of the electrically elicited blink reflex in humans. To optimize differentiation between real conditioned responses and stimulus-independent EMG activity, we developed an algorithm which is fully automated and independent of a possible bias of an examiner. In a first step the algorithm decides whether a subject fulfills the criteria of a successful learning process or not. The second step quantifies the learning process. For quantification of the learning process, the following parameters were calculated: number of conditioned responses, onset of conditioning, time and amount of maximal conditioning, speed of conditioning and speed of habituation. According to our criteria, 80% of the healthy volunteers acquired conditioned responses. There is an age-related decline in eyeblink classical conditioning. Analysis of patient groups with different types of lesions will further improve our knowledge and understanding of pathways involved in learning processes in humans. The proposed new algorithm of data analysis takes less than 10 s on a standard computer, is more sensitive and more specific in detecting conditioned responses and, therefore, may further improve the value and reliability of the eyeblink conditioning paradigm in clinical research.

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically. The facial nerve motor neurography was abnormal in 17 of 19 HMSN I patients and in both HMSN III patients, revealing moderate to marked conduction slowing in both the extracranial and intracranial nerve segments, along with variable reductions of compound muscle action potential (CMAP) amplitudes. The facial nerve conduction slowing paralleled that of limb nerves, but was not associated with clinical dysfunction of facial muscles, because none of the HMSN I patients had facial palsy. Conduction slowing was most severe in the HMSN III patients, but only slight facial weakness was present. In GBS, conduction slowing was less marked, but facial weakness exceeded that in HMSN patients in all cases. We conclude that involvement of the facial nerve is common in HMSN I and HMSN III. It affects the intra- and extracranial part of the facial nerve and is mostly subclinical.

Facial palsy in Heerfordt's syndrome: electrophysiological localization of the lesion.

Heerfordt's syndrome is characterized by fever, uveitis, swelling of the parotid gland, and facial nerve palsy and represents a variety of neurosarcoidosis. Since the first description of the syndrome, discussion about the lesion site has been controversial and has included the assumption of direct nerve compression by parotid gland swelling or a lesion within the facial canal in light of observations of accompanying taste disturbance. We report on a 26-year-old man with typical Heerfordt's syndrome who developed bilateral facial nerve palsy. Electrical and magnetic stimulation of the whole facial motor path provided strong evidence for a pathological process that: (i) began in the cerebellopontine angle; (ii) spread distally into the facial canal; and (iii) could be characterized by proximal demyelination. The patient recovered completely within 6 weeks under immunosuppressive therapy with steroids.