Journal of Neurology, Neurosurgery & Psychiatry Short reports

Dissecting the Gilles de la Tourette spectrum: a factor analytic study on 639 patients

2011-11-07T19:23:09-08:00

Background

Recent studies using quantitative methods, such as principal component factor analysis, hierarchical cluster analysis and latent class analysis have suggested that Gilles de la Tourette syndrome (GTS) should no longer be considered a unitary condition as in current classification systems.

Objective

To identify quantitative components of GTS symptomatology using a large, well characterised cohort of singleton individuals with GTS in order to inform future genetic studies with more homogeneous phenotypes.

Methods

Principal component factor analysis with oblique rotation was used to analyse symptom data from a sample of 639 patients recruited at two tertiary referral centres using identical schedules during the period 1980–2008.

Results

Three Factors were identified: (1) complex motor tics and echo-paliphenomena; (2) attention deficit and hyperactivity symptoms plus aggressive behaviours; and (3) complex vocal tics and coprophenomena. Obsessive compulsive behaviours loaded significantly on the first two factors. The three factors accounted for 48.5% of the total symptomatic variance.

Conclusions

GTS is a phenotypically heterogeneous condition encompassing simple tics, specific complex tics and associated behavioural problems. The results, coupled with previous findings, identified a clinical continuum of complex tics, hyperactivity/impulsivity symptoms and semantically relevant utterances and gestures. A better characterisation of the GTS phenotypes will help to identify susceptibility genes.

Delayed experience of volition in Gilles de la Tourette syndrome

Moretto, G., Schwingenschuh, P., Katschnig, P., Bhatia, K. P., Haggard, P. — 2011-11-07T19:23:09-08:00

Gilles de la Tourette's syndrome (TS) is a neuropsychiatric movement disorder characterised by the presence of multiple tics. Tics have an unusual, intermediate status between voluntary and involuntary movements. This ambiguity might involve not just a disorder of movement generation but also an abnormality of voluntary experience. Here the experience of voluntary movements in adult patients with TS is investigated and compared with healthy controls. A group of adult TS patients and age matched control participants estimated the time of conscious intention to perform a simple keypress movement and movement onset. Patients with TS showed a delayed experience of intention relative to controls whereas estimates of the actual movement onset were similar for patients and controls. These data suggest an abnormal experience of volition in patients with TS. Delayed volition could either be an additional intrinsic feature of the syndrome or it could reflect a cognitive strategy to limit motor excitability, and thus tic generation, during voluntary action.

Structural neuroanatomy of face processing in frontotemporal lobar degeneration

Omar, R., Rohrer, J. D., Hailstone, J. C., Warren, J. D. — 2011-11-07T19:23:10-08:00

Impairments of face processing occur frequently in frontotemporal lobar degeneration (FTLD) but the neuroanatomical basis for these deficits has seldom been studied systematically. Here a prospective voxel based morphometry study is described addressing the neuroanatomy of two key dimensions of face processing—face identification and facial emotion recognition—in a single cohort of 32 patients with FTLD (19 with frontal variant and 13 with temporal variant FTLD). For the FTLD group as a whole, face identification was positively associated with grey matter in the right anterior fusiform gyrus while recognition of angry expressions was positively associated with grey matter in the bilateral insula cortex. FTLD provides a perspective on the neuroanatomy of face processing that is complementary to focal lesion and normal functional imaging work.

Mutations in TGFBR2 gene cause spontaneous cervical artery dissection

2011-11-07T19:23:10-08:00

Mutations in the genes encoding transforming growth factor β receptors 1 and 2 (TGFBR1 and TGFBR2) have recently been associated with hereditary connective tissue disorders with widespread vascular involvement, including arterial dissection. To determine whether mutations in these genes cause spontaneous cervical artery dissection (sCAD), all coding exons of TGFBR1 and TGFBR2 were sequenced in 56 consecutive patients with sCAD. Novel TGFBR2 disease causing mutations were found in two patients. The two mutations were the pK327R substitution affecting the kinase domain of TGFBR2 and the pC138R substitution falling in the extracellular domain of the protein, involved in TGFβ binding and signalling. No TGFBR1 mutation was found. The findings indicate that TGFBR2 gene mutations are responsible for sCAD in 3.6% (95% CI 0.0 to 8.4) of cases, have implications in understanding the role of TGFβ signalling in the pathogenesis of sCAD and emphasise the importance of considering molecular characterisation of the TGFBR2 gene in these patients, regardless of the presence of clinical features suggestive of hereditary connective tissue disorders.

Maximal subthalamic beta hypersynchrony of the local field potential in Parkinson's disease is located in the central region of the nucleus

de Solages, C., Hill, B. C., Yu, H., Henderson, J. M., Bronte-Stewart, H. — 2011-11-07T19:23:10-08:00

A pathological marker of Parkinson's disease is the existence of abnormal synchrony of neuronal activity within the beta frequency range (13–35 Hz) in the subthalamic nucleus (STN). Recent studies examining the topography of this rhythm have located beta hypersynchrony in the most dorsal part of the STN. In contrast, this study of the topography of the local field potential beta oscillations in 18 STNs with a 1 mm spatial resolution revealed that the point of maximal beta hypersynchrony was located at 53±24% of the trajectory span from the dorsal to the ventral borders of the STN (corresponding to a 3.0±1.6 mm depth for a 5.9±0.75 mm STN span). This suggests that maximal beta hypersynchrony is located in the central region of the nucleus and that further investigation should be done before using STN spectral profiles as an indicator for guiding placement of deep brain stimulation leads.

Once-weekly risedronate for prevention of hip fracture in women with Parkinson's disease: a randomised controlled trial

Sato, Y., Iwamoto, J., Honda, Y. — 2011-11-07T19:23:10-08:00

Background

Incidence of a fracture, particularly in the hip joint, is high in Parkinson's disease (PD), owing to the immobilisation-induced bone resorption and vitamin D deficiency with reduced bone mineral density (BMD). The authors previously demonstrated the lowered incidence of hip fractures in PD by daily administration of risedronate and vitamin D.

Methods

This randomised, double-blind, placebo-controlled study was conducted to determine the efficacy of 17.5 mg once-weekly risedronate in the prevention of hip fracture in women with PD. Patients were randomly assigned to 17.5 mg risedronate once a week (n=136) or a placebo (n=136) combined with daily 1000 IU of ergocalciferol. Incidence of hip fractures was compared between the two groups during the 2-year follow-up.

Results

Hip fractures occurred in 15 patients in the placebo group and 3 patients in the risedronate group. The RR for hip fractures in the risedronate group as compared with the placebo group was 0.20 (95% CI 0.06 to 0.66). In the risedronate group, serum calcium levels decreased during the follow-up, while the levels in the placebo group increased. BMD increased by 3.4% in the risedronate group and decreased by 3.2% in the placebo group (p<0.01).

Conclusions

Treatment with once-weekly risedronate and ergocalciferol prevents hip fractures in older women with PD.

Antiglycine-receptor encephalomyelitis with rigidity

2011-11-07T19:23:10-08:00

Background

Glycine receptor antibodies (GlyR-ab) were reported in a patient with progressive encephalomyelitis with rigidity and myoclonus (PERM).

Methods

Three additional patients were clinically described. GlyR-ab was detected with a cell-based assay of HEK293 cells transfected with the α1 subunit of the GyR.

Results

A 33-year-old woman presented with diplopia, dysphagia and gait ataxia that improved in 5 weeks. Then, she developed a typical stiff-person syndrome (SPS) that resolved with corticosteroids, but relapsed 17 months later with a stiff limb syndrome. After treatment with intravenous immunoglobulins (IVIG), she has been asymptomatic for 8 years. A 60-year-old man developed, dysphagia, diplopia, left facial palsy and right trigeminal hypoaesthesia in a few days, followed by muscular rigidity, corticospinal signs, myoclonic jerks and severe dysautonomia. He developed seizures and suffered a cardiac arrest that left him in a persistent vegetative state. A 48-year-old man presented with leg rigidity and frequent spells of trismus, muscle spasms followed by opisthotonus and diaphoresis. The symptoms were antedated by pruritus of the left scapulae, right arm and T11–T12 dermatome. At the same time he became progressively more aggressive with emotional irritability. He also developed dysgeusia (metallic taste) and severe concurrent behavioural changes and diurnal hypersomnia. Only the rigidity and the spasms improved after therapy.

Conclusions

The clinical picture associated with GlyR-ab is wider than the classical view of PERM. GlyR-ab should be examined in patients with core symptoms of muscle rigidity and spasms atypical for SPS.