Transcranial Doppler findings in antiphospholipid syndrome.

INTRODUCTION: Transcranial Doppler is a method that enables the assessment of different cerebral hemodynamic parameters. It also allows for the evaluation of the presence of right-to-left circulation shunts (RLS) and for the detection of microembolic signals (MESs), which might be associated with an increased risk of cerebrovascular events. For instance, the presence of MESs on transcranial Doppler in patients with systemic lupus erythematous (SLE) and antiphospholipid syndrome (APS) is associated with an increased risk of stroke. Therefore, transcranial Doppler could be a useful tool for stroke risk stratification in these patients. OBJECTIVE: Our objective was to evaluate transcranial Doppler cerebral mean blood flow velocities as well as the presence of MESs and RLS in patients with antiphospholipid syndrome and SLE. PATIENTS AND METHODS: Twenty-two patients with primary APS (PAPS), 24 patients with secondary APS (SAPS), 27 patients with SLE without APS and 21 healthy controls were evaluated. Clinical and epidemiological data were compiled from medical charts, and all subjects underwent transcranial Doppler examination with breath-holding index calculation. Both middle cerebral arteries were monitored for 60 min for the detection of MESs. RLS was investigated with agitated saline injected as a bolus. RESULTS: There were no significant differences in mean blood flow velocities among the groups. MESs were more frequently found in patients with SLE when compared with controls and patients with APS (SLE: 17.4%, SAPS: 4.3%, PAPS: 0%, controls: 0%, p = 0.03). Anticoagulant therapy was more frequently used in the APS group (PAPS: 81.8%, SAPS: 75.2%, SLE: 1.7%, p < 0.001). Patients with APS had a higher frequency of RLS when compared with volunteers (63.6% versus 38.1%, p = 0.05). Breath-holding index values tended to be lower in patients with SAPS than in control subjects and patients with PAPS and SLE ( p = 0.06). CONCLUSIONS: Patients with APS had a higher frequency of RLS than healthy controls. This finding alerts to the importance of cardiac investigation in patients with stroke and APS, because further therapies such as RLS occlusion might eventually add protection. The higher frequency of MES in patients with SLE could suggest an effect of anticoagulant therapy on MES prevention, more frequently used in patients with APS.

Autonomic dysfunction in hereditary spastic paraplegia type 4.

BACKGROUND AND PURPOSE: SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was to determine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations. METHODS: Thirty-four molecularly confirmed SPG4 patients were recruited in a multicenter cross-sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age- and gender-matched healthy controls using non-parametric tests. P values <0.05 were considered significant. RESULTS: In the SPG4-HSP group, there were 18 men with a mean age of 47.7 ± 12.6 years. SCOPA-AUT scores were similar between patients and controls (P = 0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, P = 0.05). Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, P < 0.001, and 64% vs. 0%, P = 0.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the SPG4-HSP group. CONCLUSION: Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small post-ganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous system.

Neurologic manifestations of antiphospholipid syndrome.

Neurological involvement in antiphospholipid antibody syndrome (APS) is common, and its occurrence increases morbidity and mortality. Patients may present variable neurological involvement, such as cerebrovascular disease, cognitive dysfunction, headache, seizures, movement disorders, multiple sclerosis-like syndrome, transverse myelitis and ocular symptoms. Most neurological manifestations are associated with thrombosis of the microcirculation or of large vessels; nonetheless, there is compelling evidence suggesting that, in some cases, symptoms are secondary to an immune-mediated pathogenesis, with direct binding of aPL on neurons and glia. Herein we describe clinical characteristics and management of neurological APS manifestations.

Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness.

Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. Mutations in PNPLA6 also cause human spastic paraplegia characterized by motor neuron degeneration. Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration, including Leber congenital amaurosis and Oliver McFarlane syndrome. PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness.

Clinical correlates of olfactory dysfunction in spinocerebellar ataxia type 3.

Olfactory dysfunction is a very common and early sign in neurodegenerative disorders, but few data are already available in hereditary ataxias. Our aim was to evaluate the sense of smell in patients with molecular-proven spinocerebellar ataxia type 3 (SCA3). Forty-one patients with SCA3 and 46 control subjects were studied. The sense of smell was tested using the Sniffin's Sticks (SS-16). We also evaluated Mini-Mental State Examination (MMSE) and non-cerebellar symptoms, such as parkinsonism, dystonia, and restless legs syndrome (RLS). The SCA3 group had significantly lower SS-16 scores than controls (11.5 ± 2.4 vs 12.8 ± 1.5, p = 0.003). Multiple linear regression analyses, controlling for age, sex, education, cigarette smoking, and MMSE scores, showed that SCA3 (p = 0.021), sex (p = 0.003) and MMSE scores (p = 0.002) had significant regression coefficients. All the variables taken together were significantly associated with the SS-16 scores (p ≤ 0.001). Although MMSE scores and female sex were stronger predictors of the SS-16 scores than SCA3, subjects with SCA3 had lower scores on the SS-16, regardless of sex or MMSE scores. Additionally, MMSE scores, sex and presence of RLS were the best predictors of SS-16 scores. Overall, our results strengthen that the sense of smell is significantly reduced in patients with SCA3 and that sex, MMSE scores and RLS also influence the SS-16 scores.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family / Ataxia espástica autossômica recessiva de Charlevoix-Saguenay (ARSACS): aspectos clínicos e de neuroimagem típicos em uma família brasileira

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.

A ataxia espástica autossômica recessiva de Charlevoix-Saguenay (ARSACS) é doença degenerativa do sistema nervoso, caracterizada por ataxia associada a espasticidade, entre outras manifestações neurológicas, de início na infância. A doença tem alta prevalência na região de Quebec, no Canadá. Muitos relatos de ARSACS têm sido descritos fora do Canadá nas últimas décadas. Nesse artigo, relatamos a primeira descrição dos aspectos clínicos e de neuroimagem típicos em uma família brasileira com provável diagnóstico de ARSACS.

Brain SPECT imaging in Sydenham's chorea.

The objective of the present study was to determine whether brain single-photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males, 8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of 740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the remaining four were normal. The six patients with abnormal results were females and their data were not correlated with severity of symptoms. Patients with abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days) compared to those with normal SPECT (mean of 85 days) but this difference did not reach statistical significance. Brain SPECT can be a helpful method to determine abnormalities of the basal ganglia in SC patients but further studies on a larger number of patients are needed in order to detect the phase of the disease during which the examination is more sensitive.

Brain SPECT imaging in Sydenham's chorea

The objective of the present study was to determine whether brain single-photon emission computed tomography (SPECT) imaging is capable of detecting perfusional abnormalities. Ten Sydenham's chorea (SC) patients, eight females and two males, 8 to 25 years of age (mean 13.4), with a clinical diagnosis of SC were submitted to brain SPECT imaging. We used HMPAO labeled with technetium-99m at a dose of 740 MBq. Six examinations revealed hyperperfusion of the basal ganglia, while the remaining four were normal. The six patients with abnormal results were females and their data were not correlated with severity of symptoms. Patients with abnormal brain SPECT had a more recent onset of symptoms (mean of 49 days) compared to those with normal SPECT (mean of 85 days) but this difference did not reach statistical significance. Brain SPECT can be a helpful method to determine abnormalities of the basal ganglia in SC patients but further studies on a larger number of patients are needed in order to detect the phase of the disease during which the examination is more sensitive

Median nerve sep after a high medullary lesion: preserved N18 and absent P14 components. Case report

Median nerve SEPs recorded from patient with a high medullary lesion are described. The lesion involved the anteromedial and anterolateral right upper third of the medulla, as documented by MRI. Forty one days after the lesion, left median nerve SEP showed preserved N18 and absent P14 and N20 components; stimulation of the right median nerve evoked normal responses. These findings agree with the proposition that low medullary levels are involved in the generation of the N18 component of the median nerve SEP.