Correction to: The Italian Dystonia Registry: rationale, design and preliminary findings.

In the original article, Gina Ferrazzano was affiliated to Department of Neurology and Psychiatry, Neuromed Institute IRCCS, Sapienza University of Rome, Pozzilli, Italy.The corrected affiliation should be: Neuromed Institute IRCCS, Pozzilli, IS, Italy.

The Italian Dystonia Registry: rationale, design and preliminary findings.

The Italian Dystonia Registry is a multicenter data collection system that will prospectively assess the phenomenology and natural history of adult-onset dystonia and will serve as a basis for future etiological, pathophysiological and therapeutic studies. In the first 6 months of activity, 20 movement disorders Italian centres have adhered to the registry and 664 patients have been recruited. Baseline historical information from this cohort provides the first general overview of adult-onset dystonia in Italy. The cohort was characterized by a lower education level than the Italian population, and most patients were employed as artisans, builders, farmers, or unskilled workers. The clinical features of our sample confirmed the peculiar characteristics of adult-onset dystonia, i.e. gender preference, peak age at onset in the sixth decade, predominance of cervical dystonia and blepharospasm over the other focal dystonias, and a tendency to spread to adjacent body parts, The sample also confirmed the association between eye symptoms and blepharospasm, whereas no clear association emerged between extracranial injury and dystonia in a body site. Adult-onset dystonia patients and the Italian population shared similar burden of arterial hypertension, type 2 diabetes, coronary heart disease, dyslipidemia, and hypothyroidism, while hyperthyroidism was more frequent in the dystonia population. Geographic stratification of the study population yielded no major difference in the most clinical and phenomenological features of dystonia. Analysis of baseline information from recruited patients indicates that the Italian Dystonia Registry may be a useful tool to capture the real world clinical practice of physicians that visit dystonia patients.

Neurophysiology of the pelvic floor in clinical practice: a systematic literature review.

Neurophysiological testing of the pelvic floor is recognized as an essential tool to identify pathophysiological mechanisms of pelvic floor disorders, support clinical diagnosis, and aid in therapeutic decisions. Nevertheless, the diagnostic value of these tests in specific neurological diseases of the pelvic floor is not completely clarified. Seeking to fill this gap, the members of the Neurophysiology of the Pelvic Floor Study Group of the Italian Clinical Neurophysiology Society performed a systematic review of the literature to gather available evidence for and against the utility of neurophysiological tests. Our findings confirm the utility of some tests in specific clinical conditions [e.g. concentric needle electromyography, evaluation of sacral reflexes and of pudendal somatosensory evoked potentials (pSEPs) in cauda equina and conus medullaris lesions, and evaluation of pSEPs and perineal sympathetic skin response in spinal cord lesions], and support their use in clinical practice. Other tests, particularly those not currently supported by high-level evidence, when employed in individual patients, should be evaluated in the overall clinical context, or otherwise used for research purposes.

Polio Patients in Northern Italy, a 50 Year Follow-up.

BACKGROUND: Poliomyelitis was before the immunization an important medical problem. Nowadays polio prior patients (PP) suffer from polio sequelae or have developed post-polio-syndrome (PPS) with increasing paresis, pain and fatigue. OBJECTIVES: To analyze the medical situation 50 years after acute polio. The degree of paresis was compared between the recovery 1952-1961 and 2012.The prevalence of patients fulfilling the criteria for PPS was estimated. METHOD: The study was performed in Italy. Included were PP with rehabilitation after acute polio 1952-1961 and in 2012. During the years PP underwent yearly evaluation. A thorough neurological examination was performed in 2012. A telephone interview with questions concerning pain, paresis, fatigue, walking aids and concomitant diseases was performed in 2012. The patients were divided in two groups, if they fulfilled the criteria for PPS or not. RESULTS: Included were 67(94%) patients receiving rehabilitation after acute poliomyelitis and 2012. 78% were walkers, half of the PPS used wheelchair. Eight out of ten suffered from pain. Four out of ten fulfilled the PPS criteria. Pain was slightly more common in PPS. CONCLUSION: Female gender, fatigue and wheelchair dependency were significantly more common in PPS while pain was common in both groups.

Lies tell the truth about cognitive dysfunction in essential tremor: an experimental deception study with the guilty knowledge task.

BACKGROUND: Research conducted in the past decade challenges the traditional view that essential tremor (ET) is characterised exclusively by movement disorder, and increasingly shows that these patients have deficits in cognitive and behavioural functioning. The available evidence suggests that this impairment might arise from dysfunction in either the fronto-subcortical or cortico-cerebellar circuits. Although abnormalities in the fronto-subcortical circuits could imply difficulty in lying, no study has investigated deception in patients with ET. AIMS: To examine the cognitive functions regulating deception in patients with ET, we used a computerised task, the Guilty Knowledge Task (GKT). We also tested a group of patients with Parkinson's disease (PD), a disease associated with a known difficulty in lie production, and a group of healthy subjects (HS). RESULTS: In the GKT for deception, patients with ET responded less accurately than HS (p=0.014) but similarly to patients with PD (p=0.955). No differences between groups were found in truthful responses (p=0.488). CONCLUSIONS: Besides confirming impaired deception in patients with PD, our results show a lie production deficit in patients with ET also. These findings suggest that difficulty in lying is an aspecific cognitive feature in movement disorders characterised by fronto-subcortical circuit dysfunction, such as PD and ET. Current knowledge along with our new findings in patients with ET--possibly arising from individually unrecognised extremely mild, cognitive difficulties--should help in designing specific rehabilitative programmes to improve cognitive and behavioural disturbances in patients.

Corticospinal excitability during action observation in task-specific dystonia: a transcranial magnetic stimulation study.

Observation of actions performed by other individuals activates the onlooker's motor system in a way similar to real movement execution. The functioning of this mechanism in the pathological domain is not clear yet. The aim of this study was to explore whether action observation activates the motor system of patients affected by a task-specific form of dystonia, such as writer's cramp. Transcranial magnetic stimulation was applied over the primary motor cortex and motor evoked potentials were recorded from hand (FDI and ADM) and forearm (FCR) muscles at baseline and during observation of actions (grasping and writing) or images. Writing actions could be performed with healthy or dystonic movement patterns. Results showed a highly specific and reversed pattern of activation in the FDI muscle of the two groups. Differences between the two writing conditions were significantly opposite in the two groups: control subjects had higher activation during observation of the dystonic compared to the healthy action, whereas in patients observation of the healthy writing led to higher activation than the dystonic writing. This opposite corticospinal modulation might be explained by a different self-attribution of the observed actions in the two groups.

Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H.

BACKGROUND: Autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy type 4H (CMT4H) manifests early onset, severe functional impairment, deforming scoliosis, and myelin outfoldings in the nerve biopsy. Mutations in the FGD4 gene encoding the Rho-GTPase guanine-nucleotide-exchange-factor frabin were reported in five families. OBJECTIVE: To characterize a novel mutation in FGD4 and describe the related phenotype. METHODS: A 20-year-old woman born of healthy consanguineous parents and affected with early-onset peroneal muscular atrophy underwent standard clinical, electrophysiologic, and pathologic (sural nerve biopsy) investigations. Mutational analysis of FGD4 was performed by direct sequencing of genomic DNA. Transcriptional analysis was done by reverse transcriptase PCR on leukocyte RNA. RESULTS: The proband disclosed a moderately severe, scarcely progressive CMT, markedly slowed nerve conduction velocities, and a demyelinating neuropathy characterized by prominent myelin outfoldings. Mutational analysis disclosed a c.1762-2a>g transition in the splice-acceptor site of intron 14, which was predicted to cause a truncated frabin (p.Tyr587fsX14). CONCLUSIONS: The report confirms genetic heterogeneity of FGD4, demonstrates that CMT4H has variable functional impairment, and suggests that frabin plays a crucial role during myelin formation.

Combined effects of botulinum toxin and casting treatments on lower limb spasticity after stroke.

Optimal treatment of spasticity requires a combination of pharmacotherapy and muscle lengthening. We evaluated 13 stroke patients with equinovarus foot randomized to treatment with either botulinum toxin A (BTA) injection plus ankle-foot casting (n=6) or BTA alone (n=7). The tibialis posterior and calf muscles (range of BTA injection: 190 to 320 U) were treated in each patient. Castings were worn at night for four months. Each patient was examined before, and at two and four months after BTA injection using the static and dynamic baropodometric tests, the Modified Ashworth Scale and the 10-meter walking test. At two months, therapeutic effects were observed in both groups. At four months, the study group showed further clinical improvement, while the control group returned to baseline performance. Thus, prolonged stretching of spastic muscles after BTA injection affords long-lasting therapeutic benefit, enhancing the effects of the toxin alone.

Activation of middle-ear muscles by transcranial magnetic stimulation.

OBJECTIVES: To evaluate the reliability of transcranial magnetic stimulation in eliciting admittance changes due to activation of middle-ear muscles. METHODS: Admittance changes induced by transcranial magnetic stimulation at the inion were evaluated in eight normal subjects, two subjects with prelingual deafness and 22 patients suffering from other otological disorders characterised by absence of acoustic reflex. RESULTS: Responses showed a predominant negative peak in normal ears. Two small positive components, one preceding and the other following the negative deflection, were less consistently elicited. Only a positive wave was detected in otosclerotic subjects. Patients with tympanic membrane perforation or previous tympanoplasty with ossicular discontinuity did not show any response. CONCLUSIONS: Transcranial magnetic stimulation is able to activate both stapedius and tensor tympani muscles. In conjunction with admittance audiometry, it may represent a method of exploring the mechanics of the middle ear when acoustic reflex testing is not reliable. It can be helpful in the confirmation of stapes fixation when a severe to profound hearing loss is present.

Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease.

BACKGROUND: Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B. OBJECTIVE: To assess the etiologic role of DNM2 in CMT. METHODS: We performed a mutational screening of DNM2 exons 13 through 16 encoding the pleckstrin homology domain in a large series of CMT patients with a broad range of nerve conduction velocities and without mutations in more common genes. RESULTS: We identified two novel DNM2 mutations that cosegregated with purely axonal CMT in two pedigrees without clinical evidence of primary myopathy. CONCLUSION: Patients with axonal Charcot-Marie-Tooth disease type 2 neuropathy without mutations in more common genes should undergo investigation for DNM2 pleckstrin homology.

The role of muscle biopsy in investigating isolated muscle pain.

OBJECTIVE: To evaluate the muscle biopsy findings from 240 patients who had isolated muscle pain. METHODS: Histopathology, immunohistochemistry for dystrophin, dystrophin-related proteins, major histocompatibility complex type I, and biochemical analysis of glycolytic and mitochondrial respiratory chain enzymes were performed on muscle biopsies. An attempt was made to correlate pathologic data and clinical findings (sex, age, quality and distribution of symptoms, serum CK levels, and EMG recording). RESULTS: We have described five groups of patients based on muscle biopsy findings: 51.6% had heterogeneous myopathic abnormalities; only 19% of them had a specific myopathic picture, i.e., central nuclei myopathy, central core disease, myopathy with tubular aggregates or with trabecular fibers or abnormalities of fiber typing; 20% had signs of respiratory chain dysfunction but only one patient had a probable mitochondrial disease; 7% had a neurogenic pattern; 2.4% had a metabolic myopathy (phosphorylase or phosphofructokinase deficiency); and 19% had normal muscle biopsy. No clear-cut correlation between muscle biopsy and clinical data was observed except for those patients with a metabolic myopathy. CONCLUSIONS: The probability that a patient complaining only of muscle pain and with a normal neurologic examination has a definite muscle pathology is 2%. Only patients with sole exercise-related muscle pain and sCK seven times higher than the normal value are strongly suspected of having a metabolic myopathy. A rigorous selection of patients is needed before performing a muscle biopsy.

Hyperpyrexia-triggered relapses in an unusual case of ataxic chronic inflammatory demyelinating polyradiculoneuropathy.

The ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (ataxic-CIDP) has been recently described as a subtype of chronic ataxic neuropathy, distinguished by steroid responsiveness and relative preservation of myelinated fibres at sural nerve biopsy. We report on a case of progressive, predominantly sensory, steroid-responsive neuropathy with clinical, laboratory, electrophysiological and pathological features of this uncommon form of CIDP. Moreover, the present case displays peculiar hyperpyrexia-triggered relapses leading to transitory severe tetraparesis, bilateral facial drooping, dysphonia, dysphagia and dyspnoea, which leave clinicians with some unresolved questions.

TENS for the treatment of writer's cramp dystonia: a randomized, placebo-controlled study.

Manipulation of afferent inputs may temporarily modulate dystonic spasms. Ten patients with writer's cramp were enrolled in a double-blind, randomized, crossover study in which the effects of transcutaneous electrical stimulation (TENS) and placebo treatment were compared. Patients were evaluated using four measures of dystonic impairment. The TENS group showed a significant improvement that persisted for 3 weeks in three of the four measures.

Giant axon and neurofilament accumulation in Charcot-Marie-Tooth disease type 2E.

The axonal type 2 Charcot-Marie-Tooth disease (CMT2) is phenotypically poorly characterized. Here the authors report a family with a Pro22Ser mutation in the neurofilament-light gene (NF-L; CMT2E) manifesting electrophysiologically as the demyelinating type 1 CMT (CMT1) and pathologically as an axonopathy with giant axons and accumulation of disorganized NF. NF-L should be investigated in CMT2 as well as in CMT1 not associated with the usual genes PMP22, Cx32, and P0.

Paired transcranial magnetic stimulation for the early diagnosis of corticobasal degeneration.

OBJECTIVE: To investigate cortical excitability in patients with corticobasal degeneration (CBD) and to find a reliable diagnostic technique for differentiating CBD from Parkinson's disease (PD). METHODS: Using a paired transcranial magnetic stimulation technique, we studied motor cortex excitability at rest in 6 patients with clinically probable CBD, 10 patients with PD, and 10 normal subjects. The recovery cycle of the motor evoked potentials was tested by delivering paired magnetic stimulation over the hand area of the motor cortex at interstimulus intervals (ISIs) from 1 to 17ms. RESULTS: In patients with CBD, paired magnetic stimuli delivered at short ISIs invariably elicited enlarged test MEPs. At ISIs of 1-10ms, the conditioned test MEPs were significantly larger in patients with CBD than in control subjects; and at ISIs of 1, 2, 4, and 6ms,they were also larger in patients with CBD than in patients with PD. At the other ISIs tested, patients and control subjects had similar amplitude conditioned test responses. CONCLUSIONS: Our findings suggest that the unusual clinical manifestations of CBD might arise partly from motor cortex disinhibition. Paired magnetic stimulation could be a useful diagnostic test particularly in the early stages of the disease.

Axillary injection of botulinum A toxin in a patient with muscle cramps associated with severe axillary hyperhidrosis.

Muscle cramps may be caused by fluid and salt loss induced by diffuse or focal hyperhidrosis. Recent reports have described the efficacy of botulinum, toxin in the treatment of primary focal hyperhidrosis. Botulinum toxin inhibits sweating by blocking exocytosis of acetylcholine from presynaptic cholinergic nerve terminals. We report the case of a patient who complained of frequent muscle cramps associated with unusually severe axillary hyperhidrosis. We used botulinum toxin to treat the excessive focal sweating presuming that it would also reduce the muscle cramps. A total dose of 200 MU of botulinum A toxin (Dysport) per axilla markedly reduced sweating and cramps. The beneficial effect started four days after the injection and it was still present five months later. Treatment was repeated in the sixth month with analogous results. No side-effects were observed and no compensatory sweating occurred.

Somatosensory disinhibition in dystonia.

Despite the fact that somatosensory processing is inherently dependent on inhibitory functions, only excitatory aspects of the somatosensory feedback have so far been assessed in dystonic patients. We studied the recovery functions of spinal N13, brainstem P14, parietal N20, P27, and frontal N30 somatosensory evoked potentials (SEPs) after paired median nerve stimulation in 10 patients with dystonia and in 10 normal subjects. The recovery functions were assessed (conditioning stimulus: S1; test stimulus: S2) at interstimuls intervals (ISIs) of 5, 20, and 40 ms. SEPs evoked by S2 were calculated by subtracting the SEPs of the S1 only response from the SEPs of the response to the paired stimuli (S1 + S2), and their amplitudes were compared with those of the control response (S1) at each ISI considered. This ratio, (S2/S1)*100, investigates changes in the excitability of the somatosensory system. No significant difference was found in SEP amplitudes for single stimulus (S1) between dystonic patients and normal subjects. The (S2/S1)*100 ratio at the ISI of 5 ms did not significantly differ between dystonic patients and normal subjects, but at ISIs of 20 and 40 ms, this ratio was significantly higher in patients than in normals for spinal N13 and cortical N20, P27, N30 SEPs. These findings suggest that in dystonia there is an impaired inhibition at spinal and cortical levels of the somatosensory system which would lead to an abnormal sensory assistance to the ongoing motor programs, ultimately resulting in the motor abnormalities present in this disease.

The excitability of human cortical inhibitory circuits responsible for the muscle silent period after transcranial brain stimulation.

The silent period after transcranial magnetic brain stimulation mainly reflects the activity of inhibitory circuits in the human motor cortex. To assess the excitability of the cortical inhibitory mechanisms responsible for the silent period after transcranial stimulation, we studied, in 15 healthy human subjects, the recovery cycle of the silent period evoked by transcranial and mixed nerve stimulation delivered with a paired stimulation technique. The recovery cycle is defined as the time course of the changes in the size or duration of a conditioned test response when pairs of stimuli (conditioning and test) are used at different conditioning-test intervals. The recovery cycle of the duration of the silent period in the first dorsal interosseous (FDI) muscle during maximum voluntary contraction after transcranial magnetic stimulation was studied by delivering paired magnetic shocks (a conditioning shock and a test shock) at 120% motor-threshold intensity. Conditioning-test intervals ranged from 20-550 ms. The recovery cycle of the silent period in the FDI muscle during maximum voluntary contraction after nerve stimulation was evaluated by paired, supramaximum bipolar electrical stimulation of the ulnar nerve at the wrist (conditioning-test intervals ranging from 20 to 550 ms). Electromyographic activity was recorded by a pair of surface-disk electrodes over the FDI muscle. The recovery cycle of the silent period after transcranial magnetic stimulation delivered through the large round coil showed two phases of facilitation (lengthening of the silent period), one at 20-40 ms and the other at 180-350 ms conditioning-test intervals, with an interposed phase of inhibition (shortening of the silent period) at 80-160 ms. The conditioning magnetic shock left the size of the test motor-evoked potentials statistically unchanged during maximum voluntary contraction. Paired transcranial stimulation with a figure-of-eight coil increased the duration of the test silent period only at short conditioning-test intervals. Conditioning nerve stimulation left the silent period produced by test nerve stimulation unchanged. In conclusion, after a single transcranial magnetic shock, inhibitory circuits in the human motor cortex undergo distinctive short-term changes in their excitability, probably involving different mechanisms.