Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance: Report of four patients.

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired muscle disease presenting with subacute progression in adulthood. It can be accompanied by a monoclonal gammopathy of undetermined significance (MGUS). We describe clinical and histopathological findings of four SLONM patients with MGUS. In all patients, nemaline rod, inter-myofibrillary network disruption, atrophic changes, peripheral basophilic discoloration, vacuole without rim, and cytoplasmic body without inflammation were seen. Three out of four patients were treated with prednisolone in combination with IVIG monthly and had an appropriate response to the treatment. The optimal first-line treatment remains unclear in SLONM-MGUS, although corticosteroids plus IVIg is associated with favorable clinical response. These treatment modalities might be used as an optional treatment before autologous stem cell transplantation; however, further studies with a higher number of patients are required.

Diffusion Tensor Imaging as a Biomarker to Differentiate Acute Disseminated Encephalomyelitis From Multiple Sclerosis at First Demyelination.

BACKGROUND: There are no clinical features or biomarkers that can reliably differentiate acute disseminated encephalomyelitis from multiple sclerosis at the first demyelination attack. Consequently, a final diagnosis is sometimes delayed by months and years of follow-up. Early treatment for multiple sclerosis is recommended to reduce long-term disability. Therefore, we intend to explore neuroimaging biomarkers that can reliably distinguish between the two diagnoses. METHODS: We reviewed prospectively collected clinical, standard MRI and diffusion tensor imaging data from 12 pediatric patients who presented with acute demyelination with and without encephalopathy. Patients were followed for an average of 6.5 years to determine the accuracy of final diagnosis. Final diagnosis was determined using 2013 International Pediatric MS Study Group criteria. Control subjects consisted of four age-matched healthy individuals for each patient. RESULTS: The study population consisted of six patients with central nervous system demyelination with encephalopathy with a presumed diagnosis of acute disseminated encephalomyelitis and six without encephalopathy with a presumed diagnosis of multiple sclerosis or clinically isolated syndrome at high risk for multiple sclerosis. During follow-up, two patients with initial diagnosis of acute disseminated encephalomyelitis were later diagnosed with multiple sclerosis. Diffusion tensor imaging region of interest analysis of baseline scans showed differences between final diagnosis of multiple sclerosis and acute disseminated encephalomyelitis patients, whereby low fractional anisotropy and high radial diffusivity occurred in multiple sclerosis patients compared with acute disseminated encephalomyelitis patients and the age-matched controls. CONCLUSIONS: Fractional anisotropy and radial diffusivity measures may have the potential to serve as biomarkers for distinguishing acute disseminated encephalomyelitis from multiple sclerosis at the onset.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

Ideomotor limb apraxia as a staging tool in individuals with Alzheimer's disease (ILIAD).

BACKGROUND: Ideomotor apraxia (IMA) is known to affect individuals with Alzheimer's disease (AD). Combined with impaired cognitive function, IMA can support evidence of probable AD. However, apraxia is a condition that is difficult to diagnose. The Postural Knowledge Test (PKT), developed by Mozaz et al, was designed to easily identify limb apraxia in multiple sclerosis yet demonstrated potential utility for AD. ILIAD is a pilot study to investigate correlation between the PKT and Mini-Mental State Examination (MMSE). METHODS: Participants with mild, moderate, and severe AD were administered the MMSE by 1 examiner, followed by the PKT by a second blinded examiner. RESULTS: Seventy-seven participants with mild (25), moderate (26), and severe AD (26) met study criteria. Correlation was demonstrated between the MMSE and PKT at 0.835 among all AD groups. Correlation between MMSE and PKT-1 (transitive) and PKT-2 (intransitive) separately was 0.819 and 0.793. CONCLUSIONS: There is significant correlation between the MMSE (memory loss) and PKT (IMA). This suggests the PKT may be used in conjunction with the MMSE to aid in staging AD and to monitor disease severity. Correlation between the MMSE and separate PKT tests suggests that administration of only 1 test may be necessary clinically, saving valuable time.

Genetic Analysis of the ZNF512B, SLC41A1, and ALDH2 Polymorphisms in Parkinson's Disease in the Iranian Population.

AIMS: Parkinson's disease (PD) is one of the most common neurodegenerative disorders; its etiology includes both genetic and environmental factors and their interactions. The ZNF512B, SLC41A1, and ALDH2 genes have recently been identified as contributing to PD. In this study we investigated the association of alleles of these genes with PD in the Iranian population. METHODS: In a case-control study, rs2275294, rs11240569, and rs4767944, three single nucleotide polymorphisms in ZNF512B, SLC41A1, and ALDH2 genes, respectively, were genotyped in 490 PD patients and 490 controls. The genotype and allele frequencies were compared between the two groups using chi-square and logistic regression tests. RESULTS: A significant association between the rs11240569 polymorphism and a reduced risk of PD was found (p = 0.014, OR = 0.76, 95% CI: 0.60-0.94 for allele frequencies). We did not find any associations between PD and the rs2275294 and rs4767944 polymorphisms. CONCLUSION: The association of rs11240569 polymorphism in SLC41A1 gene with reduced risk of PD was replicated in our population.

The efficacy of the ketogenic diet on motor functions in Parkinson's disease: A rat model.

BACKGROUND: The ketogenic diet (KD), high in fat and low in carbohydrate and protein, provides sufficient protein but insufficient carbohydrates for all the metabolic needs of the body. KD has been known as a therapeutic manner intractable epilepsy. In recent years, the effectiveness of KD drew attention to the treatment of some other disorders such as Parkinson's disease (PD). This study has evaluated the efficacy of KD on motor function in Parkinsonian model of rat and compared it with pramipexole. METHODS: A total of 56 male Wistar rats weighing 200-240 g between 12 and 14 weeks of age were randomized in seven 8-rat groups as follows: Control group; sham-operated group; KD group; Parkinsonian control group; KD-Parkinsonian group; pramipexole-Parkinsonian group; and KD-pramipexole-Parkinsonian group. The results of bar test, beam traversal task test, and cylinder task test were compared between the groups. RESULTS: The mean number of ketone bodies had increased significantly in the rats blood after KD. Regarding the results of the triad tests, no statistically significant difference was found between the controls and the sham-operated group. Among the Parkinsonian rats, better results were found in KD groups compared to the non-KD group. The KD enhanced the effect of pramipexole for motor function but did not reach a statistically significant level. CONCLUSION: The KD reinforced the motor function in Parkinsonian rats in our study. When the diet was combined with pramipexole, the effectiveness of the drug increased in enhancing motor function.

The effects of white matter hyperintensities and amyloid deposition on Alzheimer dementia.

BACKGROUND AND PURPOSE: Elevated levels of amyloid deposition as well as white matter damage are thought to be risk factors for Alzheimer Disease (AD). Here we examined whether qualitative ratings of white matter damage predicted cognitive impairment beyond measures of amyloid. MATERIALS AND METHODS: The study examined 397 cognitively normal, 51 very mildly demented, and 11 mildly demented individuals aged 42-90 (mean 68.5). Participants obtained a T2-weighted scan as well as a positron emission tomography scan using (11)[C] Pittsburgh Compound B. Periventricular white matter hyperintensities (PVWMHs) and deep white matter hyperintensities (DWMHs) were measured on each T2 scan using the Fazekas rating scale. The effects of amyloid deposition and white matter damage were assessed using logistic regressions. RESULTS: Levels of amyloid deposition (ps < 0.01), as well as ratings of PVWMH (p < 0.01) and DWMH (p < 0.05) discriminated between cognitively normal and demented individuals. CONCLUSIONS: The amount of amyloid deposition and white matter damage independently predicts cognitive impairment. This suggests a diagnostic utility of qualitative white matter scales in addition to measuring amyloid levels.

Comparing the efficacy of botulinum toxin with tizanidine in upper limb post stroke spasticity.

BACKGROUND: This study evaluated the efficacy of focal intramuscular injection of botulinum (BoNT) toxin type A in comparison with oral tizanidine (TZD) in treatment of post-stroke upper limb spasticity. METHODS: This was a double-blinded randomized clinical trial that recruited 68 patients with post-stroke upper limb spasticity. Thirty-four patients received BoNT (Dysport(®)) injections in affected muscles of upper limb at the baseline and week 12. Thirty-four patients were treated with tizanidine (Sirdalude) by gradual increase in dosage of 2mg/week to reach maximum 24mg at week 12. Modified Ashworth Scale (MAS) and Action Research Arm Test (ARAT) were evaluated at the baseline, week 12 and week 24 for all the participants. RESULTS: The mean score of MAS reduced from 3.32 and 3.13 at baseline to 1.79 and 1.56 at week 24 on elbow and wrist joints, respectively (P < 0.01). However, there were only reductions from 2.79 and 2.77 to 2.32 and 2.31 (P < 0.001) in TZD group. ARAT increased from 1.79 to 10.97 (P < 0.001) in BoNT group. ARAT increased from 11.08 to 11.35 in TZD group (P = 0.026). CONCLUSION: BoNT injection was safe and effective in reducing post-stroke upper extremity spasticity in comparison with TZD.

Hemiparkinsonism-hemiatrophy syndrome.

The syndrome of hemiparkinsonism-hemiatrophy is an uncommon form of secondary Parkinsonism that presents with unilateral body Parkinsonism plus variable atrophy on the same side. Diagnosis of this syndrome needs a complete past medical history taking, as well as assessment of the familial history, clinical examination and complete paraclinical tests.The response to medical therapy has been variable in various researches. This case showed a good response to the addition of a dopamine agonist to levodopa therapy.