Brain imaging in Kufs disease type B: case reports.

BACKGROUND: The clinical traits of Kufs disease (KD) type B (CLN13), an adult-onset neuronal ceroid lipofuscinosis (NCL), are well established according to the neurological features of the cases reported with mutations in CTSF. The neuroradiological characteristics of this uncommon disease have not yet been outlined. CASE PRESENTATION: We hereby report the brain MRI features in two Caucasian women who carried homozygous mutations in CTSF, providing a short review of the neuroradiological findings of other common NCLs. Together with a brain volume reduction, the two cases showed white matter hyperintensities and thinning of the corpus callosum at onset of the cognitive decline. CONCLUSION: White matter hyperintensities associated with volume reduction of the corpus callosum may be present at the beginning of the behavioural changes in CLN13 and represent further clues for searching mutations in CTSF.

Idiopathic pes cavus in adults is not associated with neurophysiological impairment in the lower limbs.

The nerve conduction characteristics of adults with idiopathic pes cavus/hammer toes have not been studied extensively. Among 2048 out-patients (59.5 ± 13.9 years) referring to a laboratory of Neurophysiology in Rome, we recruited 18 patients with idiopathic pes cavus (61.3 ± 12.5 years). Fifty-four age/sex-matched controls were also studied. No nerve conduction differences were observed between patients with and without cavus foot (p > 0.05). The absence of deep tendon reflexes and slight muscle weakness and hypotrophy in the lower limbs were more common in subjects with cavus foot deformity than in controls (p < 0.001). Adult patients with idiopathic pes cavus/hammer toes do not differ from healthy controls from a neurophysiological standpoint, but they could show minor signs of clinical impairment, such as lower limb weakness, hypotrophy and areflexia.

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

BACKGROUND: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. METHODS: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. RESULTS: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. CONCLUSIONS: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. CLINICALTRIALSGOV, NUMBER: NCT01037777 and NCT00136630 for the French patients.

Strategies adopted by cerebellar ataxia patients to perform U-turns.

Cerebellar ataxia is associated with unsteady, stumbling gait, and affected patients report a high rate of falls, particularly during locomotor tasks. U-turns (180° turns while walking) require a high level of coordination in order to completely reverse the body trajectory during ongoing motion, and they are particularly challenging for patients with cerebellar ataxia. The aim of this study was to investigate the kinematic strategies adopted by ataxic patients when performing U-turns. Nine ataxic patients and ten controls were analysed as they performed 180° turns to the right while walking. We evaluated the following aspects: centre of mass velocity, body rotation, number of steps needed to complete the task, step length and step width, lower limb joint kinematics and segmental reorientation. Compared with controls, the ataxic patients showed slower deceleration and re-acceleration of the body, needed more steps to complete the U-turn, showed markedly reduced step length and were unable to modulate step width between steps. Furthermore, the patients adopted an extended joint rather than a flexed joint turning strategy, and the degree of knee flexion was found to be negatively correlated with the number of falls. Ataxic patients show an abnormal U-turn in comparison to age-matched healthy subjects. Some of the observed alterations are indicative of a primary deficit in limb-joint coordination, whereas others suggest that patients choose a compensatory strategy aimed at reducing the instability.

Sudden stopping in patients with cerebellar ataxia.

Stopping during walking, a dynamic motor task frequent in everyday life, is very challenging for ataxic patients, as it reduces their gait stability and increases the incidence of falls. This study was conducted to analyse the biomechanical characteristics of upper and lower body segments during abrupt stopping in ataxic patients in order to identify possible strategies used to counteract the instability in the sagittal and frontal plane. Twelve patients with primary degenerative cerebellar ataxia and 12 age- and sex-matched healthy subjects were studied. Time-distance parameters, dynamic stability of the centre of mass, upper body measures and lower joint kinematic and kinetic parameters were analysed. The results indicate that ataxic patients have a great difficulty in stopping abruptly during walking and adopt a multi-step stopping strategy, occasionally with feet parallel, to compensate for their inability to coordinate the upper body and to generate a well-coordinated lower limb joint flexor-extensor pattern and appropriate braking forces for progressively decelerating the progression of the body in the sagittal plane. A specific rehabilitation treatment designed to improve the ability of ataxic patients to transform unplanned stopping into planned stopping, to coordinate upper body and to execute an effective flexion-extension pattern of the hip and knee joints may be useful in these patients in order to improve their stopping performance and prevent falls.

Gait pattern in inherited cerebellar ataxias.

Our aim was to perform a comprehensive analysis of the global and segmental features of gait in patients with genetically confirmed inherited ataxias. Sixteen patients with autosomal dominant (spinocerebellar ataxia, SCA1 or 2) or recessive (Friedreich's ataxia, FRDA) ataxia were studied. We used a motion analysis system to record gait kinematic and kinetic data. We measured the mean values of global (time-distance parameters, COM displacement, support moment) and segmental gait parameters (joint displacement and inter-joint coordination), as both discrete and continuous variables, and their variability and correlations with International Cooperative Ataxia Rating Scale (ICARS) scores. We found a marked difference in all global gait parameters between the ataxic patients and the controls and close correlations between longer stride and stance duration and lower gait, posture and total ICARS scores. The only difference between the two patient groups was a shorter step length in the FRDA patients. As regards the segmental features, we found a significantly different waveform shape for all continuous kinematic and kinetic measures between the ataxic patients and the healthy controls, but only minor differences for the discrete measures. Intersegmental coordination evaluated using the continuous relative phase method revealed an irregular alternating joint behaviour without clear evidence of the synchronous pattern of alternating proximal/distal joint seen in healthy subjects. For almost all gait parameters we observed a markedly higher intra-subject variability in the ataxic patients versus the controls, which was strongly related to the clinical ICARS scores. Patients with chronic, progressive inherited ataxias lose the ability to "stabilize" a walking pattern that can be repeated over time. The most peculiar aspect of the gait of inherited ataxia patients, regardless the different genetic forms, seems to be the presence of increased variability of all global and segmental parameters rather than an invariant abnormal gait pattern.

Infantile childhood onset of spinocerebellar ataxia type 2.

Spinocerebellar ataxia type 2 (SCA2) is a late-onset autosomal dominant cerebellar ataxia caused by triplet CAG/CTG expansion in the ATX2 gene. The initial symptoms usually appear when subjects are in their 30s.Pediatric onset is less common and usually associated with larger triplet expansions. We here report the case of a 1-year-old girl who presented with facial dysmorphism,dystonic features, developmental delay, and retinitis pigmentosa.She was diagnosed as carrying an expanded CAG/CTG tract (92 repeats) before a molecular diagnosis of SCA2 was made in her father. Facial dysmorphism associated with developmental delay and retinitis pigmentosa in early childhood should prompt a careful family investigation for ataxia and study of ATX2.

Planned gait termination in cerebellar ataxias.

This study set out to characterise the pattern of planned gait termination in a sample of patients with cerebellar diseases. The gait termination phase was recorded, using a motion analysis system, in ten patients with primary degenerative cerebellar disease and in ten controls. The subjects were instructed to walk at different gait speeds and to stop in response to an acoustic signal. Time-distance parameters (step length, step width, double support duration, time-to-slow, stopping time, centre of mass velocity and number of steps) and stability index-related parameters (distance between the "extrapolated centre of mass" (XCoM) and centre of pressure (CoP)) were measured at both matched and self-selected gait speeds. At matched speed the patients, compared with the controls, showed a reduced step length, a greater first and second step width and used more steps to stop. At self-selected speed, almost all the parameters differed from those of the controls. Furthermore, the patients showed an increased stability index, suggesting that they need to maintain a "safety margin" between the XCoM and CoP during the gait termination. Patients develop a series of compensatory strategies in order to preserve balance during planned gait termination, e.g. increasing their step width and number of steps. Ataxic patients need to maintain a safety margin in order to avoid instability when stopping. Given the potential risk of falls when stopping, walking ataxic patients may benefit from a rehabilitation treatment focused on preserving and improving their ability to terminate gait safely.

Scuba diving is not associated with high prevalence of headache: a cross-sectional study in men.

OBJECTIVE: To study the prevalence of cephalalgia in male divers. BACKGROUND: Scuba divers work in stressing environments and have a high cerebrovascular risk, both conditions which are supposed to contribute to the genesis of cephalalgia. However, no study assessed expressly the prevalence of cephalalgia in divers, to date. METHODS: We enrolled 201 professional male scuba divers (41.0 ± 7.2 years) and controls (41.1 ± 7.2 years), and the risk ratio and its corresponding 95% confidence of suffering from cephalalgia was calculated. RESULTS: We found that 16% of divers and 22% of matched controls were affected by cephalalgia (P > .05), accounting for a risk ratio of 0.71 (95% CI 0.47-1.07). Divers reported fewer attacks per month (1.8 ± 0.7, n = 32) with regard to controls (2.5 ± 1.8, n = 45) (P = .02), but no differences concerning age at onset and severity were detected (P > .05). Divers suffered from migraine, migraine with aura and tension headache as much as controls. CONCLUSION: Scuba diving, an intense physical activity characterized by cerebral micro-vascular distress, is not associated with cephalalgia, as a whole, or migraine, tension headache or migraine with aura, more commonly than in a matched, non-diving, population. A longitudinal study may disclose if diving may act as a protective factor in the occurrence of crises of cephalalgia.

Iatrogenic selective lesion of the median nerve at the elbow.

A lesion of the median nerve may occur as a consequence of a compression by a haematoma or for a direct damage of the axons caused by a needle insertion. To date, no investigation reported a very selective lesion of the median nerve at the elbow, with the suffering limited only to the fibres for the first digit. A 53 year-old left-handed violinist underwent an arterial blood gas drawing. The patient complained immediately of an electrical shock impression going down the arm, followed by pin sensation into the first finger. A tingling sensation associated with numbness in the first fingertip and difficulty in the index-thumb pinch became progressively evident. The ENG-EMG findings showed an impairment mainly of the sensory fibres innervating the first digit and a drop of the motor action potential amplitude when the nerve was stimulated at the elbow. We reported a very partial lesion of the left median nerve at the elbow in a violinist who had a selective involvement of the fibres for his first digit. Even minimal lesions of the median nerve may impair severely the quality of life of patients.

Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.e., Italy), and establish whether there is one or more common mutation. In 25 index cases we identified 32 mutations; 22 are novel, including 9 nonsense, 3 small deletions, 4 insertions, 1 in/del, 1 small duplication, 1 missense, 2 splice-site, and for the first time a large genomic rearrangement. This brings the total number of SPG11 mutated patients in the SPATAX collection to 111 cases in 44 families and in 17 isolated cases, from 16 Countries, all assessed using homogeneous clinical criteria. While expanding the spectrum of mutations in SPG11, this larger series also corroborated the notion that even within apparently homogeneous population a molecular diagnosis cannot be achieved without full gene sequencing.

An inherited large-scale rearrangement in SACS associated with spastic ataxia and hearing loss.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is a neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy, with or without mental retardation. The array of mutations in SACS has expanded worldwide after the first description in Quebec. We herein report the identification of an unconventional SACS mutation, a large-scale deletion sized approximately 1.5 Mb encompassing the whole gene, in two unrelated patients. The clinical phenotype of the patients was similar to more canonical ARSACS cases, though it is was complicated by the unusual presence of hearing loss. Our findings suggest that a "microdeletion" on chromosome 13q12 represents a novel allelic variant associated with ARSACS, stressing the need for an expanded testing in molecular diagnostic laboratories.

Contrast echocardiography and migraine in divers with patent foramen ovale.

BACKGROUND: It has been proposed that the patent foramen ovale (PFO) may be associated with migraine, in particular migraine with aura. However, it is not clear whether paradoxical embolism triggers crises of headache. Cerebral embolization is provoked in subjects with PFO through contrast echocardiography, a safe method to diagnose the presence of foramen ovale pervium. METHODS: Twenty-four men practicing diving, an activity characterized by increased prevalence of PFO and migraine, underwent trans-thoracic echocardiography with contrast solution, composed of saline and air mixture and checked for the occurrence of migraine in the following 24 hours. RESULTS: A PFO (five of minimal size, i.e. visible only during Valsalva, one of small and two of medium size) was detected in 8/24 divers (33%). No one reported headache over the 24 hours after the procedure. DISCUSSION: Our preliminary data suggest that cerebral micro-embolism, provoked by contrast echocardiography, does not systematically trigger migraine crises when a minimal-to-medium sized patent foramen ovale is present.