To investigate the agreement between manually and automatically generated tracts from diffusion tensor imaging (DTI) in patients with temporal lobe epilepsy (TLE). Whole and along-the-tract diffusivity metrics and correlations with patient clinical characteristics were analyzed with respect to tractography approach. We recruited 40 healthy controls and 24 patients with TLE who underwent conventional T1-weighted imaging and 60-direction DTI. An automated (Automated Fiber Quantification, AFQ) and manual (TrackVis) deterministic tractography approach was used to identify the uncinate fasciculus (UF) and parahippocampal white matter bundle (PHWM). Tract diffusion scalar metrics were analyzed with respect to agreement across automated and manual approaches (Dice Coefficient and Spearman correlations), to side of onset of epilepsy and patient clinical characteristics, including duration of epilepsy, age of onset and presence of hippocampal sclerosis. Across approaches the analysis of tract morphology similarity revealed Dice coefficients at moderate to good agreement (0.54 - 0.6) and significant correlations between diffusion values (Spearman's Rho=0.4–0.9). However, within bilateral PHWM, AFQ yielded significantly lower FA (left: Z = 4.4, p<0.001; right: Z = 5.1, p<0.001) and higher MD values (left: Z=-4.7, p<0.001; right: Z=-3.7, p<0.001) compared to the manual approach. Whole tract DTI metrics determined using AFQ were significantly correlated with patient characteristics, including age of epilepsy onset in FA (R = 0.6, p = 0.02) and MD of the ipsilateral PHWM (R=-0.6, p = 0.02), while duration of epilepsy corrected for age correlated with MD in ipsilateral PHWM (R = 0.7, p<0.01). Correlations between clinical metrics and diffusion values extracted using the manual whole tract technique did not survive correction for multiple comparisons. Both manual and automated along-the-tract analyses demonstrated significant correlations with patient clinical characteristics such as age of onset and epilepsy duration. The strongest and most widespread localized ipsi- and contralateral diffusivity alterations were observed in patients with left TLE and patients with HS compared to controls, while patients with right TLE and patients without HS did not show these strong effects. Manual and AFQ tractography approaches revealed significant correlations in the reconstruction of tract morphology and extracted whole and along-tract diffusivity values. However, as non-identical methods they differed in the respective yield of significant results across clinical correlations and group-wise statistics. Given the absence of excellent agreement between manual and AFQ techniques as demonstrated in the present study, caution should be considered when using AFQ particularly when used without reference to benchmark manual measures.
Non–motor symptoms are increasingly recognised in Parkinson9s disease contributing to the morbidity and disability. Are non–motor symptoms specific to PD, and can we identify which they are, or are they a feature of other chronic neurological conditions?
Backgound
The non–motor symptoms of Parkinson9s disease (PD) occur frequently, and are often under recognised, yet may have a significant impact on quality of life.
Design/Methods
We performed an observational case–control questionnaire study comparing patients with Parkinson9s disease, epilepsy, and spouse/carers controls. Three validated questionnaires were used. The Non–motor Symptoms Questionnaire (NMSQuest); Hospital Anxiety and Depression Scale; Liverpool Adverse Events Profile Scale (AEP). The control group of spouse/carers also completed the Scale of Quality of Life of Care–Givers. Other information collected included age, gender, disease duration, Hoehn & Yahr (for PD patients), and Liverpool Epilepsy Impact Scale for epilepsy patients. Patients were recruited from the regional Movement and Epilepsy clinics. Patients with cognitive impairment were excluded (MMSE<24).
Results
Completed questionnaires were received from 129 PD, 60 epileptic patients, and 140 spouse/carer controls. Non–motor symptoms total scores were significantly higher in PD patients than epileptics when controlling for age, sex and duration of disease (p<0.05). There was no significant difference between the patient groups for anxiety and depression and the total AEP score.In individual items on the NMSQuest, constipation, incontinence, delusions and hallucinations, dreams, insomnia and sweating did not differ between the patient groups. Whilst restless legs, acting out dreams, memory, dribbling, and bladder urgency were highly significantly worse in the PD patients compared to epileptics (p<0.001).The patients had a significantly worse score on the NMSQuest compared to spouse/carers for all items except insomnia and swelling.
Conclusion
Non–motor symptoms are a feature of PD, and are more common and more frequent than in patients with epilepsy and spouse/carers. In other chronic neurological conditions non–motor symptoms may occur. However, in PD patients certain non–motor symptoms and their severity appear to characterise the condition and may significantly impact on quality of life.
A 58-year-old lady with waxing and waning of non-specific symptoms including fatigue, dizziness, hearing loss and unsteady gait for 15 months, became acutely confused 12 h prior to presentation. On admission to a district hospital she was feverish and unresponsive. Her travel history consisted of visits to Argentina, Chile and the Outer Hebrides. CT of the brain was normal. Lumbar puncture demonstrated a lymphocytic pleocytosis of 500 cells, protein of 1 g/l, a low glucose ratio with negative cytology and viral PCR (including herpes simplex 1 and 2). MRI revealed multiple abnormal areas of high signal on T2 fluid attenuated inversion recovery sequencing within the cerebellum, temporal lobes and periventricular areas. Western blotting of serum and cerebrospinal fluid for Borrelia burgdoferi were both positive. She was treated with cefuroxime and aciclovir and within 24 h she was alert and responsive. She received 4 weeks of cefuroxime in total and made a good recovery.
Facial onset sensory motor neuronopathy (FOSMN) is a rare, slowly progressive bulbar onset motor and sensory neuronopathy. Described only in 2006, it is still under–recognised with fewer than 20 cases reported in world literature. Although there are marked similarities to classical bulbar onset MND, FOSMN is set apart clinically by the striking facial–onset sensory deficits with subsequent development of motor deficits, slow evolution in a rostral–caudal direction and a much better prognosis.
Methods
We present three cases from three different regions of the UK. Case 2 was presented at ABN 2011. A 62–year–old man presented with a three–year history of perioral paraesthesia, numbness and slurred speech, followed by upper limb weakness, fasciculations and muscle cramps. He was dysarthric, anosmic and anegusic. Sensation to pin prick and fine touch was decreased in all divisions of the trigeminal nerve bilaterally with absent corneal reflexes bilaterally. The tongue was atrophic; fasciculations were noted in the tongue and the upper limbs. Electrophysiological studies revealed widespread neurogenic changes without evidence of polyneuropathy. Extensive investigations for alternative aetiologies were unyielding. A 38–year–old woman presented with bilateral facial sensory loss. Over the following ten years she developed weakness and sensory loss in her arms and legs. Fasciculations and flaccid weakness were noted throughout her upper limbs, and there was finger drop of her fourth and fifth digits. Sensation to pinprick was reduced in her face, upper trunk and arms with some involvement distally in the legs. Proprioception and vibration sensation was normal. Horizontal saccades were slow. Electrophysiological studies revealed widespread denervation. No alternate aetiology was found on extensive testing. There was no response to repeated courses of intravenous immunoglobulin over 12 months. A 69–year–old man presented with a four–month history of numbness affecting his left cheek gradually progressing to involve his right cheek, jaw, forehead and tongue. Speech was dysarthric with reduced sensation to pinprick and soft touch in all divisions of the trigeminal nerve as well as the tongue. Over the next five years he developed wasting and fasciculations of his tongue with widespread wasting and brisk reflexes of the upper limb muscles. No alternate aetiology was detected after extensive tests. Treatment with steroids and subsequently with intravenous immunoglobulin was of no benefit.
Conclusions
These three cases are similar to previously published reports and support the hypothesis that FOSMN is a sporadic, degenerative disorder distinct from typical MND.1 TDP–43 mutations were reported by some but are not universally present. Early, accurate diagnosis is essential to allow appropriate counselling regarding the prognosis, which is much better than for bulbar onset MND with survival often exceeding ten years.
A 58-year-old lady who had waxing and waning nonspecific symptoms including fatigue and unsteadiness for 15 months became acutely confused 12 h prior to presentation. Her travel history prior to presentation consisted of visits to Argentina, Chile and the Outer Hebrides. On admission to a district hospital she was pyrexial and unresponsive. CT was normal, she had a lymphocytic pleocytosis of 500, protein of 1 g, a low glucose ratio and type 2 oligoclonal bands, CSF cytology and HSV were negative. Baseline blood tests, tumour markers, autoimmune screening including paraneoplastic antibodies and voltage-gated potassium channel antibodies were also negative. Magnetic resonance imaging revealed multiple abnormal areas of high signal on T2 FLAIR sequencing within the cerebellum, temporal lobes, and periventricular areas. Western blotting of serum and CSF for Borrelia burgdoferi were both positive. She was treated with cefuroxime and acyclovir and within 24 h she was alert and responsive. She received 4 weeks of cefuroxime in total and made a good recovery. Lyme disease should be considered in patients with acute meningoencephalitis preceded by nonspecific waxing and waning symptoms even if a tick bite or erythema is not recalled.
Polytherapy is increasingly common because of the large number of new Anti Epileptic Drugs (AED). We carried out a study to determine if polytherapy has more adverse effects (AE) than monotherapy.
Methods
We compared three groups: monotherapy (n=186), polytherapy (n=325) and control subjects no taking AED (n=65). We used the Liverpool Adverse Event Profile (LAEP) to ascertain AE and to calculate the total AE score. We also recorded the frequency of refractory epilepsy, depression subscores on the LAEP and drug doses.
Results
The mean LAEP scores were significantly higher in polytherapy (45.56, CI=44.36 to 46.76) than in monotherapy (42.29, CI=40.65 to 44.02) and controls (33.25, CI=31.05 to 35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED. The frequencies of symptoms reported as always or sometimes a problem were as follows: tiredness (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems 76%/63.2%/29.2% and difficulty concentrating 68%/63.9%/30.8%. The proportion of seizure free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this was not statistically significant.
Conclusion
Patients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.
To evaluate whether the lines occasionally detected on clinical magnetic resonance (MR) images are genuine hippocampal layers, a formalin fixed hippocampal specimen was scanned using T2 weighted sequences at 7 Tesla (voxel dimensions 0.064×0.064×1 mm) and at 1.5 Tesla (voxel dimensions: 0.156×0.156×1 mm) and compared with the results of histological examination. In addition, a healthy volunteer was scanned with a T2 weighted sequence at 1.5 Tesla (voxel dimensions: 0.469×0.469×2 mm). On 7 Tesla images hippocampal layers and the granule cell layer of the dentate were visible. On 1.5 Tesla images of the specimen, the hippocampal layers were again identified, but the granule cell layer of the dentate was not detectable. On 1.5 Tesla images of the hippocampus in vivo, 3 layers could be distinguished in the hippocampus on some slices. These mainly represented the alveus, pyramidal cell layer and stratum radiatum. A dark line consisting of a few pixels possibly represented the dentate gyrus. Our results show that the lines occasionally detected on clinical MR images are likely to be real hippocampal layers. However, the resolution currently used in clinical imaging (typically 0.469×0.469×2 mm or lower) is not sufficient for the detection of all hippocampal layers. For the reliable detection of all hippocampal layers on MR images an increase by a factor of approximately 20 would be necessary.
A 48-year-old man presented with numbness in fingers and diplopia 1 week after a flu-like illness. He made a full recovery but 8 years later developed progressive and disabling sensory ataxia. He had superimposed acute flare-ups with numbness, double vision and ptosis, all following infections. A blood test showed antidisialosyl antibodies including GD1b, GD3, GT1b and GQ1b in keeping with the diagnosis of chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and antidisialosyl antibodies (CANOMAD). Initial treatment with monthly courses of intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days every 4 weeks helped temporarily but there were marked disabling fluctuations of symptoms. With IVIg 0.6 g/kg/day weekly his symptoms are stable. He remains mobile and has no eye symptoms without need for any other medication. This case demonstrates that weekly IVIg infusions instead of one 5-day course monthly may be able to avoid fluctuations of symptoms in CANOMAD.
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