video_4_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.asf

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

Video_2_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.WMV

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

Video_3_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.WMV

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

Video_1_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.MP4

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

Video_4_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.WMV

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

video_3_Adult Periodic Alternating Nystagmus Masked by Involuntary Head Movements.asf

<p>Acquired periodic alternating nystagmus (PAN) describes a horizontal jerk nystagmus that reverses its direction with a predictable cycle, and is thought to arise from lesions involving the brainstem and cerebellum. We report a 20-year-old patient with PAN who presented with an acute vertiginous episode and developed an involuntary head movement that initially masked the PAN. The involuntary head movements were abolished with a subtherapeutic dose of botulinum toxin to the neck muscles. We propose that the head movements initially developed as a compensatory movement to the nystagmus, to maintain visual fixation in the presence of the underlying nystagmus, and became an entrained involuntary behavior. This case highlights the importance of disambiguating psychogenic from organic pathology as this may have clinical therapeutic implications, in this case resolution of the most disabling symptom which was her head oscillations, leading to improved day-to-day function despite PAN.</p

Successful quantification of mHTT in PBMCs from 8ml whole blood in HD.

<p>These data confirm that mHTT levels in leukocytes are higher at more advanced disease stages. Assay A (mHTT N-terminus assay) was used to selectively quantify mHTT: S/B, signal over background. A) Sample set 1 (mean of 2 replicates); (B) Sample set 2 (mean of 3 replicates).</p

Schematic diagram showing the capture and detection antibody pairs for each assay.

<p>The huntingtin amino acid residue epitope to which the antibodies bind are shown (not to scale). Poly-Q, polyglutamine region; Poly-P, proline rich region. Details of the antibodies are given in the text below.</p

Box plots showing average polyglutamine independent HTT levels across patient subgroups.

<p>(S/B: Signal / Background) No significant differences are seen between HTT species levels and disease stage, other than a difference in C-terminal HTT between Moderate and Early HD patients. (A) Distribution of Mid Region HTT (Assay C) in sample group 1. (B) Distribution of Mid Region HTT (Assay C) in sample group 2. (C) Distribution of polyglutamine-independent N terminal HTT (Assay B) in sample group 2. (D) Distribution of C terminal HTT (polyglutamine-independent Assay D) in sample group 2.</p

Association between HTT species level (S/B: Signal/Background, mean replicated samples) and disease burden score; adjusted for age, sex and CAG.

<p>(A) HTT mid region in sample set 1, (B) N-terminal HTT in sample set 2, (C) HTT mid region in sample set 2, (D) C-terminal HTT in sample set 2). Circles = premanifest, triangles = Early, squares = Moderate.</p