Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social and communication skills, narrow interests, and repetitive behavior. It is known that the cerebellum plays a vital role in controlling movement and gait posture. However, recently, researchers have reported that the cerebellum may also be responsible for other functions, such as social cognition, reward, anxiety, language, and executive functions. METHODS: In this study, we ascertained volumetric differences from cerebellar lobular analysis from children with ASD, ASD siblings, and typically developing healthy controls. In this cross-sectional study, a total of 30 children were recruited, including children with ASD (N = 15; mean age = 27.67 ± 5.1 months), ASD siblings (N = 6; mean age = 17.5 ± 3.79 months), and typically developing children (N = 9; mean age = 17.67 ± 3.21 months). All the MRI data was acquired under natural sleep without using any sedative medication. We performed a correlation analysis with volumetric data and developmental and behavioral measures obtained from these children. Two-way ANOVA and Pearson correlation was performed for statistical data analysis. RESULTS: We observed intriguing findings from this study, including significantly increased gray matter lobular volumes in multiple cerebellar regions including; vermis, left and right lobule I-V, right CrusII, and right VIIb and VIIIb, respectively, in children with ASD, compared to typically developing healthy controls and ASD siblings. Multiple cerebellar lobular volumes were also significantly correlated with social quotient, cognition, language, and motor scores with children with ASD, ASD siblings, and healthy controls, respectively. CONCLUSIONS: This research finding helps us understand the neurobiology of ASD and ASD-siblings, and critically advances current knowledge about the cerebellar role in ASD. However, results need to be replicated for a larger cohort from longitudinal research study in future.

Automatic Classification of Healthy Subjects and Patients With Essential Vocal Tremor Using Probabilistic Source-Filter Model Based Noise Robust Pitch Estimation.

Essential voice tremor (EVT) is a voice disorder resulting from dyscoordination within the laryngeal musculature. A low-frequency fluctuations of fundamental voice frequency or the strength of excitation amplitude is the main consequence of the disorder. The automatic classification of healthy control and EVT is useful tool for the clinicians. A typical automatic EVT classification involves three steps. The first step is to compute the pitch contour from the speech. The second step is to compute the features from the pitch contour, and the final step is to use a classifier to classify the features into healthy or EVT. It is shown that a high-resolution pitch contour estimated from the glottal closure instants (GCIs) is useful for EVT classification. The HPRC estimation can be very poor in the presence of noise. Hence, a probabilistic source filter model based noise robust GCI detection is used for HPRC estimation. The Empirical mode decomposition based feature extraction is used followed by a support vector machine classifier. The EVT classification performance is evaluated using recordings from 45 subjects. The proposed method is found to perform better than the baseline techniques in eight different additive noise conditions with six SNR levels.

Assessment of Voice Outcomes Post Chemo-Radiotherapy in Non-Laryngeal Head & Neck Cancers Using Electroglottography and Voice Symptom Scale (VoiSS) Questionnaire.

BACKGROUND: Laryngeal toxicity (LT) following concurrent chemo-radiotherapy (CCRT) for non-laryngeal head & neck cancers(NLHNC) has been inadequately studied. Electroglottography (EGG), a non-invasive technique for objective quantification of LT, measures the change in electrical impedance generated by glottic closure. AIM: Objective and subjective assessment of acute LT post-CCRT in NLHNC. MATERIALS AND METHODS: A prospective study on 30 NLHNC patients, treated with CCRT; 66-70Gy/33- 35fractions with weekly Cisplatin. Flexible laryngoscopic examination and EGG were performed at baseline, 6weeks, and 3months post-CCRT; Grades of LT and contact quotients(CQ) were documented. Patientreported outcomes of voice-related quality of life(QoL) performed at the same intervals, using a 30-item Voice Symptom Scale (VoiSS) questionnaire. STATISTICAL ANALYSIS: Results of continuous measurements were studied by mean +/- standard deviation. Analysis of variance (ANOVA) was used for comparison of pretreatment and post-treatment results in more than two groups. Significance was assessed at 5% level ofsignificance. Post- hoc analysis has been done using Tukey-Krammer method for multiple comparisons. Correlation analysis was performed using Pearson correlation test. RESULTS: 26/30 patients completed CCRT; 14 were available at 6weeks; 10 at 3months post-CCRT for analysis. At 6 weeks, 3/14(21.5%) patients had Grade II LT; 11/14(78.57%) had grade III. At 3months, 2/10(20%) had Grade I, 6/10(60%) had grade II but 2/10(20%) had worsened to grade IV. Mean CQ at baseline was 50.77 +/- 5.55; which decreased at 6 weeks to 48.56 +/- 4.66 and further at 3months to 45.56 +/- 4.66 (>0.05) suggestive of glottic hypo-adduction. VoiSS responses showed a significant impact on QoL in all three domains at six weeks and three months post-CCRT, compared to baseline (P < 0.0001). CONCLUSION: Electroglottography is a potential tool to quantify acute LT post CCRT. Patient-reported outcomes may not correlate to the objective measures of laryngeal toxicity and require separate recording and reporting. A larger sample size would be required to draw further significant correlations. Key Words: Electroglottography; laryngeal toxicity; head neck cancer; voice; chemo-radiotherapy.

Emerging behavioral and neuroimaging biomarkers for early and accurate characterization of autism spectrum disorders: a systematic review.

The possibility of early treatment and a better outcome is the direct product of early identification and characterization of any pathological condition. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication, restricted, and repetitive patterns of behavior. In recent times, various tools and methods have been developed for the early identification and characterization of ASD features as early as 6 months of age. Thorough and exhaustive research has been done to identify biomarkers in ASD using noninvasive neuroimaging and various molecular methods. By employing advanced assessment tools such as MRI and behavioral assessment methods for accurate characterization of the ASD features and may facilitate pre-emptive interventional and targeted therapy programs. However, the application of advanced quantitative MRI methods is still confined to investigational/laboratory settings, and the clinical implication of these imaging methods in personalized medicine is still in infancy. Longitudinal research studies in neurodevelopmental disorders are the need of the hour for accurate characterization of brain-behavioral changes that could be monitored over a period of time. These findings would be more reliable and consistent with translating into the clinics. This review article aims to focus on the recent advancement of early biomarkers for the characterization of ASD features at a younger age using behavioral and quantitative MRI methods.

Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ preservation at the cost of preservation of function. Vocal cords, being within the field of irradiation, undergo acute and chronic changes which adversely impacts the patients' voice. AIMS: To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70 Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3 months post-CCRT. Statistical analysis of the parameters using ANOVA and Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%]) developed Grade III toxicity. On AA, both increase and decrease in mean F0 from baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14 available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for both genders; jitter and shimmer, and NHR values maintained an increase (P > 0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and mapping of vocal toxicity induced by CCRT.

Comprehensive management of psychogenic dysphonia: a case illustration.

UNLABELLED: Psychogenic dysphonia refers to the loss of voice, in the absence of apparent structural or neurological pathology. It is a disorder seen more often in women and is usually associated with significant life events and emotional difficulties that may lead to conflict over speaking. Therapeutic interventions in voice disorders recommend the adoption of a multidisciplinary approach to treatment. The following is a case illustration of a 50-year-old married lady with dysphonia and significant marital difficulties. LEARNING OUTCOMES: The case demonstrates the psychological issues in the onset and maintenance of psychogenic voice disorders. It also emphasizes the use of a multidisciplinary approach consisting of cognitive behavioural strategies, pharmacological inputs and voice therapy. The case illustration will also help the reader to focus on cultural issues relevant in the development of problems and the need to address these in psychotherapeutic interventions, as well as difficulties that are likely to be encountered in therapeutic interventions.

Madras motor neuron disease (MMND): clinical description and survival pattern of 116 patients from Southern India seen over 36 years (1971-2007).

Madras motor neuron disease (MMND), MMND variant (MMNDV) and Familial MMND (FMMND) have a unique geographic distribution predominantly reported from Southern India. The characteristic features are onset in young, weakness and wasting of limbs, multiple lower cranial nerve palsies and sensorineural hearing loss. We describe the clinical features and survival pattern in 116 patients with Sporadic MMND, MMND variant and FMMND. A retrospective review of patients' medical records for clinical manifestations, electromyography, imaging, audiological and histopathology findings was performed. Over 36 years (1971 to 2007) 116 patients (men: 59; women: 57) particularly hailing from Southern India were seen. Mean age of onset was 15.8+/-7.9 years. Predominant initial manifestations were impaired hearing with wasting and weakness of distal limb muscles and pyramidal dysfunction. All patients had clinical and/or audiological evidence of hearing impairment. Patients with MMNDV in addition had optic atrophy. The overall mean survival duration was 334.9+/-27.9 months. Thus, Madras motor neuron disease is clinically a distinct entity with features of amyotrophic lateral sclerosis but with young age of onset and presence of auditory neuropathy. Studies to look for environmental and genetic basis of this intriguing disease are necessary to find the causation of this rare disorder.

Familial Madras motor neuron disease (FMMND): study of 15 families from southern India.

Madras motor neuron disease (MMND) and Madras motor neuron disease variant (MMNDV) have an unique geographic distribution with concentration of majority of cases in the southern states of India. They have the characteristic features of onset in young, weakness and wasting of the limbs, multiple cranial nerve palsies particularly involving the 7th, 9th to 12th and sensorineural hearing impairment. In addition, all patients with MMNDV have bilateral optic atrophy. During the past 32 years, a total of 104 patients were diagnosed to have MMND and among these 25 patients with the familial form were further evaluated. In this report, we describe the clinical features of these 25 patients diagnosed to have familial Madras motor neuron disease (FMMND) or familial Madras motor neuron disease variant (FMMNDV), belonging to 15 families hailing from southern India. There were 10 patients diagnosed to have FMMND and 15 with FMMNDV. There were 14 males and 11 females with mean age at onset of 13.0+/-6.2 years and mean duration of illness of 73.6+/-74.0 months. Notably, the occurrence of MMNDV in the familial group (15 of 25 patients) was significantly more as compared to occurrence in the group with sporadic MMND (SMMND) [12 of 79 patients] (p=0.0002).