Myasthenia gravis, atypical polyneuropathy and multiple autoimmune phenomena in the same patient, with HLA-immunogenetic profile expectable for Greek chronic inflammatory demyelinating polyneuropathy: a case report.

PURPOSE: The comorbidity of myasthenia gravis (MG), with other autoimmune disorders like systemic lupus erythematosus (SLE), is relatively frequent but the co-occurrence with chronic inflammatory demyelinating polyneuropathy (CIDP) along with various autoimmune manifestations in the absence of thymoma is of extreme rarity. Our aim is to report a case of a woman who presented the concomitant appearance of MG, axonal sensory-motor polyneuropathy and hepatitis that may indicate an underlying pathogenetic link among the different autoimmune disorders. MATERIALS AND METHODS/RESULTS: We present a case of a 54-year-old woman, with a generalized MG and a chronic sensory-motor polyneuropathy, hypothyroidism, anaemia, hepatitis, livedo reticularis and facial flush, of assumed autoimmune background, like SLE, although with persistent negative ANA antibodies, from the beginning and through the whole following years. The Human Leukocyte Antigen (HLA)-DRB1 genotyping showed a profile of alleles (DRB1*11:01/11:04) compatible with CIDP of mainly female gender in Greece and frequencies close to those of Sjogren's syndrome and scleroderma's in the Greek population. The diagnostic problems, the atypical clinical, electrophysiological and immunological features are discussed, along with the rarity of the case, with this exceptional combination of autoimmune manifestations, which could be truly associated under the clinical umbrella of a systemic disease, like SLE. However, our patient did not ever fulfil the SLE criteria. CONCLUSIONS: To raise awareness among clinicians about the exceptional combination of autoimmune manifestations driven by a specific HLA background.

Multimodal Neurophysiological and Neuroimaging Evidence of Genetic Influence on Motor Control: A Case Report of Monozygotic Twins.

Considering genetic influence on brain structure and function, including motor control, we report a case of right-handed monozygotic twins with atypical organization of fine motor movement control that might imply genetic influence. Structural and functional organization of the twins' motor function was assessed using transcranial magnetic stimulation (TMS), fMRI with a motor-task paradigm, and diffusion tensor imaging (DTI) tractography. TMS revealed that both twins presented the same unexpected activation and inhibition of both motor cortices during volitional unilateral fine hand movement. The right ipsilateral corticospinal tract was weaker than the left contralateral one. The motor-task fMRI identified activation in the left primary motor cortex and bilateral secondary motor areas during right-hand (dominant) movement and activation in the bilateral primary motor cortex and secondary motor areas during left-hand movement. Based on DTI tractography, both twins showed a significantly lower streamline count (number of fibers) in the right corticospinal tract compared with a control group, which was not the case for the left corticospinal tract. Neither twin reported any difficulty in conducting fine motor movements during their activities of daily living. The combination of TMS and advanced neuroimaging techniques identified an atypical motor control organization that might be influenced by genetic factors. This combination emphasizes that activation of the unilateral uncrossed pyramidal tract represents an alternative scheme to a "failure" of building a standard pattern but may not necessarily lead to disability.

Differences in Pain Perception Between Men and Women of Reproductive Age: A Laser-Evoked Potentials Study.

Objective: We investigated differences in pain perception between men and women of reproductive age by using Laser-Evoked Potentials (LEPs). Design, Setting, Subjects: Forty-four right-handed healthy volunteers (19 males/25 females), aged 30­40 years were studied. A CO2 laser generated three series of 10 thermal pulses (4.5 W) on the radial aspect of the dorsum of the left hand. A recording montage for late LEPs was used, and the potentials of each series of stimuli were averaged to calculate mean latency and amplitude for each subject. Volunteers scored verbally pain intensity (Numerical rating scale [NRS]; 0­10). Three series of 10 numbers were averaged for calculation of mean NRS score. Methods: LEP peak-to-peak amplitude, latency, and NRS scoring were compared between genders, and correlations between LEP amplitude/latency and NRS scores were assessed. Results: Data from 44 subjects were analyzed. LEP amplitudes differed significantly (P < 0.001) between men (24.2 ± 6.0 µV) and women (38.9 ± 15.28 µV), while no difference was found for latency (156.5 ± 8.6 versus 160.4 ± 19.8 ms, P = 0.42) or NRS score (2.6 ± 1.5 versus 2.4 ± 1.4, P = 0.63), respectively. Menstrual cycle phase did not influence LEP parameters (P = 0.59 for amplitude and P = 0.69 for latency) or NRS score (P = 0.95). No significant correlation was found between latency or amplitude and NRS score (P = 0.43 and P = 0.90, respectively). Conclusions: Our results demonstrate a significant gender-related difference in LEP amplitudes with lower mean values in men, while no difference was found in LEP latencies or in subjective pain ratings. Further research is required to clarify the clinical significance of the above experimental findings.

Mutational analysis of Greek patients with suspected hereditary neuropathy with liability to pressure palsies (HNPP): a 15-year experience.

There has been limited information from population studies regarding the overall frequency of the common 1.5-Mb 17p11.2 deletion and even scarcer data regarding the overall frequency of PMP22 micromutations in patients with a clinical suspicion of hereditary neuropathy with liability to pressure palsies (HNPP). We have analysed 100 consecutive Greek patients referred for HNPP genetic testing over a 15-year period to our Neurogenetics Unit in Athens, a reference centre for all regions of Greece. All patients were screened for the 1.5-Mb deletion and a selected subgroup of deletion-negative patients for PMP22 micromutations. Mutation-positive and mutation-negative patients were compared for various clinical parameters. In total, 54 mutation-positive patients were identified. In index cases, the deletion frequency was 47.8%, and the PMP22 micromutation frequency was 2.2%. Within mutation-positive patients, the common deletion represented 95.7% and PMP22 micromutations 4.3% of cases. Two previously reported PMP22 micromutations (c.364_365delCC and c.79-2A>G) were detected. HNPP index cases had a 2.8-1 male-to-female ratio, similar to mutation-negative patients. A typical phenotype (recurrent or isolated palsies) was present in 82.4% of symptomatic HNPP cases, significantly higher than mutation-negative patients. Sensitivity of proposed electrophysiological diagnostic criteria for HNPP was calculated at 95.7% and specificity at 80.5%. In conclusion, the common HNPP deletion accounts for ∼50% and PMP22 micromutations for ∼2% of cases in a large consecutive cohort of patients with suspected HNPP. The mutational and phenotypic spectrum of HNPP is similar in the Greek population compared with other populations. Proposed electrophysiological diagnostic criteria perform satisfactorily in everyday clinical practice.

Validation of the Greek Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain.

BACKGROUND: The Douleur Neuropathique 4 questionnaire (DN4) was developed by the French Neuropathic Pain Group and is a simple and objective tool, primarily designed to screen for neuropathic pain. The aim of our study is to validate the DN4 in the Greek language. METHODS: The study was set up as a prospective observational study. Two pain specialists independently examined patients and diagnosed them with neuropathic, nociceptive, or mixed pain, according to the International Association for the Study of Pain (IASP) definitions. A third and a fourth physician administered the DN4 questionnaire to the patients. RESULTS: Out of the 237 patients who met our inclusion criteria and had identical diagnoses regarding the type of pain, 123 were diagnosed with neuropathic, 59 with nociceptive, and 55 with mixed pain. Among patients with identical diagnoses of neuropathic or nociceptive pain, using a receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.92. A cutoff point of equal or greater than 4 resulted in a sensitivity of 93% and a specificity of 78%. Among patients suffering from pain with neuropathic element (neuropathic or mixed pain) or pain with no neuropathic element (nociceptive pain), using a ROC curve analysis, the AUC was 0.89. A cutoff point of equal or greater than 4 resulted in a sensitivity of 89% and a specificity of 78%. CONCLUSION: The Greek version of DN4 is a valid tool for discriminating between neuropathic and nociceptive pain conditions in daily practice.

Diabetic neuropathy: comparison between Bangladeshi immigrants and Greek-born subjects.

The aim of this study was to compare Bangladeshi immigrants with diabetes to native Greeks with diabetes and to distinguish the different risk factors for polyneuropathy (PN) in the two ethnic groups. Subjects were recruited from the outpatient diabetic clinic of a general hospital. A total of 111 Bangladeshi immigrants (97 men and 14 women of mean age 47 years) and 101 native Greeks (82 men and 19 women of mean age 49 years) were included in the study. Sex, mean age, age at diabetes diagnosis, and diabetes duration did not differ between the two groups. PN was diagnosed in 53 (48%) Bangladeshi and in 59 (58%) Greek patients (p = 0.12). Large fiber neuropathy was less prevalent among Bangladeshis (18%) than in Greeks (53%) (p < 0.01). Small fiber neuropathy on the contrary were more frequent in Bangladeshis (18% vs. 7%) (p < 0.02). Regarding the risk factors for PN, Greek patients were taller, with higher BMI, and smoked more cigarettes (p < 0.001). They were also treated with more anti-lipid and antihypertensive agents. The higher percentage of SFN in Bangladeshi was mainly a result of the significantly greater incidence of erectile dysfunction (ED) in their group (68 Bangladeshi vs. 38 Greek men). It is well known that there are many causes of ED aside from SFN which were not evaluated in this study. Thus this conclusion should be taken with caution.

Jitter Remains Stable Throughout a Single Fiber EMG Session in Healthy and Myasthenic Muscles.

Fatigability is the hallmark of myasthenia gravis (MG). It is not clear, however, whether there is an analogous increase in jitter during the course of a single fiber electromyography (SFEMG) session. The individual jitter values of all potentials of 76 normal and 44 myasthenic orbicularis oculi muscles were assigned a rank number according to their temporal order in which they were collected and linear regression was performed to determine if the slope of the regression line was significantly different from zero. Control and MG subjects displayed rather flat linear regression lines with non-significant positive or negative slopes. Accordingly, ROC analysis yielded areas under the curve near 0.5. We conclude that there is no systematic jitter increase during the collection of 20 potential pairs in a typical SFEMG session.

Carpal tunnel syndrome: associations between risk factors and laterality.

AIMS: The investigation of the association between known risk factors and laterality in patients with carpal tunnel syndrome (CTS). PATIENTS AND METHODS: 130 consecutive subjects with CTS only, or mainly, in the left hand were compared with 130 consecutive subjects with CTS only, or mainly, in the right hand. The following parameters were recorded: age, sex, job, handedness, hand mainly used in daily activities, BMI, diabetes mellitus, thyroid dysfunction, wrist trauma and connective tissue diseases. RESULTS: A left dominant hand was independently associated with 13-fold higher odds for left-hand CTS, while a right dominant hand had 5-fold higher odds for right-hand CTS. Right-hand CTS was more frequent in younger subjects and females. CONCLUSION: Older age, higher BMI and diabetes mellitus were more prevalent in patients with bilateral CTS. Age and BMI were independently associated with bilateral CTS.

Intramuscular fibre conduction velocity and muscle fascicle length in human vastus lateralis.

Muscle fascicle length and muscle fibre conduction velocity (MFCV) are thought to be important parameters for power performance. It might be expected that faster muscle fibre conduction velocities would compensate for longer fascicle lengths to increase the speed of action potential propagation along the elongated fibres. However, the relationship between muscle fascicle length and MFCV remains unknown. The aim of the present study was to explore the relationship between average vastus lateralis MFCV and average fascicle length. In 17 moderately trained, healthy, male, physical education students (age, 23.4 ± 3.1 years; body height, 178 ± 5.5 cm; body mass, 82.7 ± 6.9 kg; body mass index, 24.6 ± 1.5 kg·m-2) resting MFCV was measured with intramuscular microelectrodes while muscle architecture was evaluated with ultrasonography. Fascicle length was highly correlated with total MFCV (r = 0.923, p = 0.000), maximum MFCV (r = 0.949, p = 0.000), and MFCV of the fastest (r = 0.709, p = 0.001), but not of the slowest fibres (r = 0.131, p = 0.616). No significant correlations were also found between vastus lateralis thickness or fascicle angle with any of MFCV parameters (r = 0.145-0.430; R2 < 0.130; p > 0.05). These data indicate that average MFCV is associated with average fascicle length in vastus lateralis muscle in different individuals. It seems that participants with longer fascicle lengths have also higher MFCVs.

A strong linear relationship between Turns/Amplitude peak ratio and ratio at maximal effort.

In EMG interference pattern analysis, the peak value of turns to mean amplitude ratio [peak(T/A)] is an established clinically significant marker, but its calculation requires specific software available only in few EMG apparatuses. On the contrary, the turns to mean amplitude ratio obtained at maximal muscle contraction (T/Amax) is easily calculated but less well standardized. We aimed to quantitatively assess the association between T/Amax and peak(T/A). Data were derived from 642 muscle contractions (Nc) from 270 consecutive patients (Np) who underwent EMG at our laboratory (software Dantec Keypoint, QEMG) from May 2015 to September 2016 and had interference patterns obtained from at least one of the following muscles: triceps-lateral head, brachioradialis, extensor digitorum communis and biceps. Statistics were calculated separately for normal and neurogenic muscles. Peak(T/A) was calculated by the built-in "peak ratio" function. T/Amax was calculated by the built-in Interference Pattern analysis function. The ratio with the highest amplitude was selected as T/Amax. Linear regression models provided high Pearson correlation coeffficientscoefficients (R) between peak(T/A) and T/Amax for all 4 muscles, normal or neurogenic, except a subgroup of biceps in patients aged <40y. Specifically, R were: (A) triceps normal 0.79 (Nc = 99), neurogenic 0.83 (Nc = 50) (B) brachioradialis normal 0.81 (Nc = 84), neurogenic 0.78 (Nc = 66) (C) extensor digitorum communis normal 0.72 (Nc = 92), neurogenic 0.73 (Nc = 61) (D) biceps (age > 40y) normal 0.77 (Nc = 77), neurogenic 0.67 (Nc = 62). We conclude that T/Amax has a strong linear association with peak(T/A) and, therefore, the former may be further investigated as a potentially useful quantitative diagnostic marker, especially in cases where the latter is not available.

Electromyographic Study of Thoracic Paraspinal and Rectus Abdominis Muscles in Amyotrophic Lateral Sclerosis.

PURPOSE: The aim of our study was the comparison of active denervation (fibrillation and/or positive sharp wave potentials) in thoracic paraspinal muscles with rectus abdominis in patients with definite amyotrophic lateral sclerosis. METHODS: Ninety-five consecutive patients with clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria were studied prospectively over a 5-year period. Concentric needle electromyogram was performed in thoracic paraspinal muscles, in the rectus abdominis at the T9 level, and in limb muscles. RESULTS: Active denervation was present in thoracic paraspinal muscles in 75 patients (79%) and in rectus abdominis in 62 patients (65.3%) (P = 0.02). No significant difference was found between the two muscles regarding the type of onset (bulbar, upper, and lower limbs), amyotrophic lateral sclerosis functional rating scale values, and creatine phosphokinase levels. CONCLUSIONS: Thoracic paraspinal muscles are the first to be tested in patients with amyotrophic lateral sclerosis. Absence of active denervation in T-PSM is rarely associated with active denervation in rectus abdominis.

Reliability and Validation of the Greek Version of the Boston Carpal Tunnel Questionnaire.

BACKGROUND: The Boston Carpal Tunnel Questionnaire (BCTQ) is an easy, brief, self-administered questionnaire developed by Levine et al for the assessment of severity of symptoms and functional status of patients with carpal tunnel syndrome. The aim of our study was to develop and validate the Greek version of BCTQ. METHODS: We conducted a cross-sectional study of 90 patients with idiopathic carpal tunnel syndrome. The original English version of BCTQ was adapted into Greek using forward and backward translation. Reliability was assessed by internal consistency (Cronbach α and item-total correlation) and reproducibility. Validity was examined by correlating the Boston Questionnaire scores to Canterbury severity scale for electrodiagnostic severity grading. RESULTS: The Greek version showed high reliability (Cronbach α 0.89 for Symptom Severity Scale and 0.93 for Functional Status Scale) and construct validity (Pearson correlation coefficient 0.53 for Symptom Severity Scale and 0.68 for Functional Status Scale). Test-retest were 0.75 for Symptom Severity Scale and 0.79 for Functional Status Scale ( P < .05). Receiver operating characteristic curve analysis showed that the optimal cutoff of Symptom Severity Scale for the discrimination of subjects with low electrodiagnostic severity grading than subjects with high electrodiagnostic severity grading was 1.95 with sensitivity equal to 75.5% and specificity equal to 68.3%. CONCLUSIONS: The Greek version of the BCTQ is a valid, reliable screening tool for assessment in daily practice of symptoms and functional status in patients with carpal tunnel syndrome.

Motor and extra-motor gray matter integrity may underlie neurophysiologic parameters of motor function in amyotrophic lateral sclerosis: a combined voxel-based morphometry and transcranial stimulation study.

The association between gray matter (GM) density and neurophysiologic changes is still unclear in amyotrophic lateral sclerosis (ALS). We evaluated the relationship between GM density and motor system integrity combining voxel-based morphometry (VBM) and transcranial magnetic stimulation (TMS) in ALS. We included 17 ALS patients and 22 healthy controls (HC) who underwent 3D-T1-weighted imaging. Among the ALS group, we applied left motor cortex single-pulse TMS. We used whole-brain VBM comparing ALS and HC in GM density. We also conducted regression analysis to examine correlations between GM density and the following TMS parameters: motor evoked potential (MEP)/M ratio and central motor conduction time (CMCT). We found significantly decreased GM density in ALS patients in several frontal, temporal, parietal/occipital and cerebellar regions (p < 0.001 uncorrected; cluster-extent threshold k = 100 voxels per cluster). With regards to TMS parameters, ALS patients showed mostly increased MEP/M ratio and modest prolongation of CMCT. MEP/M ratio was associated with GM density in (a) rolandic operculum/inferior frontal gyrus/precentral gyrus; anterior cingulate gyrus; inferior temporal gyrus; superior parietal lobule; cuneus; superior occipital gyrus and cerebellum (positive association) and (b) paracentral lobule/supplementary motor area (negative association). CMCT was associated with GM density in (a) inferior frontal gyrus and middle cingulated gyrus (positive association) and (b) superior parietal lobule; cuneus and cerebellum (negative association). Our findings support a significant interaction between motor and extra-motor structural and functional changes and highlight that motor and extra-motor GM integrity may underlie TMS parameters of motor function in ALS patients.

Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis.

The phenotypic heterogeneity in amyotrophic lateral sclerosis (ALS) implies that patients show structural changes within but also beyond the motor cortex and corticospinal tract and furthermore outside the frontal lobes, even if frank dementia is not detected. The aim of the present study was to investigate both gray matter (GM) and white matter (WM) changes in non-demented amyotrophic lateral sclerosis (ALS) patients with or without cognitive impairment (ALS-motor and ALS-plus, respectively). Nineteen ALS-motor, 31 ALS-plus and 25 healthy controls (HC) underwent 3D-T1-weighted and 30-directional diffusion-weighted imaging on a 3 T MRI scanner. Voxel-based morphometry and tract-based spatial-statistics analysis were performed to examine GM volume (GMV) changes and WM differences in fractional anisotropy (FA), axial and radial diffusivity (AD, RD, respectively). Compared to HC, ALS-motor patients showed decreased GMV in frontal and cerebellar areas and increased GMV in right supplementary motor area, while ALS-plus patients showed diffuse GMV reduction in primary motor cortex bilaterally, frontotemporal areas, cerebellum and basal ganglia. ALS-motor patients had increased GMV in left precuneus compared to ALS-plus patients. We also found decreased FA and increased RD in the corticospinal tract bilaterally, the corpus callosum and extra-motor tracts in ALS-motor patients, and decreased FA and increased AD and RD in motor and several WM tracts in ALS-plus patients, compared to HC. Multimodal neuroimaging confirms motor and extra-motor GM and WM abnormalities in non-demented cognitively-impaired ALS patients (ALS-plus) and identifies early extra-motor brain pathology in ALS patients without cognitive impairment (ALS-motor).

Differential sensitivity of thick and thin fibers to HIV and therapy-induced neuropathy.

The study assessed HIV-related and anti-retroviral therapy-induced neuropathy in myelinated and unmyelinated nerve fibers. One hundred consecutive HIV patients were examined clinically and standard nerve conduction velocities were measured. In addition, electrically induced sympathetic skin response (SSR) was assessed in the palms and soles. The difference in delay of SSR in palms and soles (DeltaSSR) was calculated as an indirect measure of C-fiber conduction velocity. Thick fiber conduction velocities significantly decreased with age and increasing stage of the disease, whereas no effect of stage was found for DeltaSSR (p=0.6). In contrast, medication of at least one of the most known neurotoxic drugs zalcitabine, stavudine, or didanosine did not result in significantly lower conduction velocities in thick fibers (51.29+/-3.4 m/s vs. 50.86+/-3.5 m/s), but was related to an increased DeltaSSR. DeltaSSR allows an indirect measurement of C-fiber conduction velocity. In HIV this measure of unmyelinated sympathetic fibers was most sensitive to anti-viral treatment whereas conduction velocity of myelinated somatic fibers was more sensitive to disease-related neuropathy. The results suggest that HIV neuropathy preferably affects myelinated and anti-retroviral therapy unmyelinated fibers.

Presymptomatic neuromuscular disorders disclosed following statin treatment.

It is well recognized that statins affect muscular tissue adversely and that their use is associated with clinically important myositis, rhabdomyolysis, mild elevation of serum creatine kinase (CK) levels, myalgias, muscle weakness, muscle cramps, and persistent myalgias or serum CK level elevations after statin treatment is discontinued. The association between statins and the disclosure of presymptomatic metabolic myopathy is another underrated phenomenon related to statin therapy that was recently recognized in rare cases. The purpose of this report is to provide additional support for this association and to report other neuromuscular disorders that have also been seen following statin intake. The present case series illustrates that statins may act as unmasking agents in asymptomatic patients with a latent neuromuscular disorder. Thus, it may be postulated that statin intake may be a sufficient insult to precipitate neuromuscular symptoms and substantially increase muscle enzymes in presymptomatic patients with an abnormal neuromuscular substrate. In conclusion, muscular symptoms or increased serum CK levels persisting after statin treatment discontinuation should alert the clinician to pursue further diagnostic evaluations for the detection of potential underlying neuromuscular diseases.

Lack of Definite Association of Vitamin D Deficiency with Diabetic Neuropathy. Investigation in Greek and in Bangladeshi Patients.

AIM: Determination of the 25(OH) vitamin D levels in Greek-born and in Bangladeshi immigrant patients in Greece with diabetes with and without polyneuropathy. MATERIALS AND METHODS: The method for the detection and staging of polyneuropathy proposed by Dyck, 1988 was used. RESULTS: A total of 111 Bangladeshi immigrants and 101 Greek diabetic patients took part in the study. Vitamin D levels were significantly lower in Bangladeshi than in Greek diabetic patients, and were significantly lower in Greek patients with small-fiber neuropathy. In Bangladeshi patients, there was no statistically significant difference in the subgroup of patients with polyneuropathy in comparison to those without polyneuropathy. CONCLUSION: The association of vitamin D deficiency only with a small number of Greek patients with exclusively small-fiber neuropathy does not allow us to draw a definite conclusion on the role of vitamin D in the pathogenesis of diabetic neuropathy.

Characterization of a reproducible rat EAMG model induced with various human acetylcholine receptor domains.

Myasthenia gravis (MG) is usually caused by antibodies against the muscle acetylcholine receptor (AChR). Experimental autoimmune MG (EAMG) is the animal model of MG, typically induced by immunization of rodents with AChR isolated from the electric organ of Torpedo californica. We have successfully induced EAMG in Lewis rats by immunization with the extracellular domains (ECDs) of the human AChR subunits (α, ß, γ, δ and ε) expressed in yeast. Analysis of the antibody titers revealed a robust antigenic response against all the peptides, but a marked difference in their pathogenicity; the α subunit ECD was the most pathogenic, resulting in the highest percentage of affected animals. Measurements of antibody titers, electromyographic tests and quantitation of the muscle AChR content, offered further support to these findings. The EAMG models presented herein, could be used for studying subunit-specific pathogenic mechanisms, and, more importantly, as tools for the evaluation of antigen-specific therapeutic approaches, which rely on the human AChR.

Spastic paretic hemifacial contracture as a presenting feature of multiple sclerosis.

BACKGROUND: Spastic paretic hemifacial contracture (SPHC) is characterized by sustained unilateral contraction of the facial muscles associated with mild ipsilateral facial paresis. Rarely described in the context of multiple sclerosis (MS), it has never been reported as presenting symptom of MS. CASE REPORTS: Two patients developed SPHC within the context of a clinically isolated syndrome suggestive of MS. EMG revealed continuous resting activity of irregularly firing motor unit potentials, associated with impaired recruitment upon voluntary contraction. SPHC remitted fully in both patients. CONCLUSIONS: SPHC, a rare but distinct clinical and EMG entity, can occasionally be the presenting feature of MS.

Memory-related white matter tract integrity in amyotrophic lateral sclerosis: an advanced neuroimaging and neuropsychological study.

We aimed to investigate structural changes in vivo in memory-related white matter tracts (i.e., perforant pathway zone [PPZ]; uncinate fasciculus [UF]; fornix) using diffusion tensor tractography and evaluate possible associations with memory performance in nondemented patients with amyotrophic lateral sclerosis (ALS). Forty-two ALS patients and 25 healthy controls (HCs) underwent a 30-directional diffusion-weighted imaging on a 3T MR scanner, followed by tractography of PPZ, UF, and fornix and analysis of fractional anisotropy (FA), axial diffusivity and radial diffusivity (Dr). Patients were administered neuropsychological measures of verbal (list learning via Rey Auditory Verbal Learning Test [RAVLT] and prose memory via Babcock Story Recall Test) and nonverbal (Rey's Complex Figure Test) episodic memory. After correcting for multiple comparisons, ALS patients showed increased Dr in the left PPZ compared to HC. We then fitted a multivariate general linear model within ALS patients with neuropsychological measures as dependent variables and age, age2, gender, verbal IQ, and diffusion tensor tractography metrics with at least medium effect size differences between ALS and HC as independent variables. We found that (1) left PPZ FA, gender, and verbal IQ contributed to RAVLT-Total Learning; (2) left PPZ FA, left UF Dr, and gender contributed to RAVLT-Immediate Recall; and (3) left PPZ FA and left UF axial diffusivity contributed to Babcock Story Recall Test-Immediate and Delayed Recall. Advanced neuroimaging techniques verified in this study previously reported neuropathological findings regarding PPZ degeneration in ALS. We also detected a unique contribution of microstructural changes in hippocampal and frontotemporal white matter tracts on patients' memory profile.