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23


Hypothesis: The Vestibular and Cerebellar Basis of the Mal de Debarquement Syndrome

Cohen, Bernard; Yakushin, Sergei B; Cho, Catherine
The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.
PMCID:5807657
PMID: 29459843
ISSN: 1664-2295
CID: 2963232

Treatment of the Mal de Debarquement Syndrome: A 1-Year Follow-up

Dai, Mingjia; Cohen, Bernard; Cho, Catherine; Shin, Susan; Yakushin, Sergei B
The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient's rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4-5 days. During treatment, patients' heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients' ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.
PMCID:5418223
PMID: 28529496
ISSN: 1664-2295
CID: 2572212

Optic neuropathy in late-onset neurodegenerative Chediak-Higashi syndrome

Desai, Ninad; Weisfeld-Adams, James D; Brodie, Scott E; Cho, Catherine; Curcio, Christine A; Lublin, Fred; Rucker, Janet C
BACKGROUND: The classic form of Chediak-Higashi syndrome (CHS), an autosomal recessive disorder of lysosomal trafficking with childhood onset caused by mutations in LYST, is typified ophthalmologically by ocular albinism with vision loss attributed to foveal hypoplasia or nystagmus. Optic nerve involvement and ophthalmological manifestations of the late-onset neurodegenerative form of CHS are rarely reported and poorly detailed. METHODS: Case series detailing ophthalmological and neurological findings in three adult siblings with the late-onset form of CHS. RESULTS: All three affected siblings lacked features of ocular albinism and demonstrated significant optic nerve involvement as evidenced by loss of colour and contrast vision, central visual field loss, optic nerve pallor, retinal nerve fibre layer thinning by optical coherence tomography (OCT) and abnormal visual evoked potential, with severity corresponding linearly to age of the sibling and severity of neurological disease. Further, unusual prominence of a 'third line' on macular OCT that may be due to abnormal melanosomes was seen in all three siblings and in their father. Neurological involvement included parkinsonism, cerebellar ataxia and spastic paraparesis. CONCLUSIONS: This report expands the ophthalmological phenotype of the late-onset neurodegenerative form of CHS to include optic neuropathy with progressive vision loss, even in the absence of ocular albinism, and abnormal prominence of the interdigitation zone between cone outer segment tips and apical processes of retinal pigment epithelium cells on macular OCT.
PMID: 26307451
ISSN: 1468-2079
CID: 1742162

Deep Brain Stimulation for Status Dystonicus: A Case Series and Review of the Literature [Case Report]

Ben-Haim, Sharona; Flatow, Virginia; Cheung, Tyler; Cho, Catherine; Tagliati, Michele; Alterman, Ron L
BACKGROUND:Status dystonicus (SD) is a rare and potentially life-threatening complication of primary or secondary dystonia, characterized by acute worsening of dystonic movements. There is no consensus regarding optimal treatment, which may be medical and/or surgical. METHODS:We present our experience with pallidal deep brain stimulation (DBS) in 5 DYT1-positive patients with SD and provide a review of the literature to examine optimal management. RESULTS:Of the 5 patients treated with pallidal DBS, all experienced postoperative resolution of their dystonic crisis within a range of 1-21 days. Long-term follow-up resulted in 1 patient returning to preoperative baseline, 3 patients improving from baseline, and 1 patient making a complete recovery. Of the 28 SD patients (including our 5 patients) reported in the literature who were treated with DBS or ablative surgery, 26 experienced cessation of their dystonic crisis with a return to baseline function and, in most cases, clinical improvement. CONCLUSION:DBS is an effective therapeutic modality for the treatment of SD. In addition to the long-term benefits of stimulation, early and aggressive treatment may improve the overall outcome.
PMID: 27504896
ISSN: 1423-0372
CID: 4590602

Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome

Dai, Mingjia; Cohen, Bernard; Smouha, Eric; Cho, Catherine
The mal de debarquement syndrome (MdDS), a continuous feeling of swaying, rocking, and/or bobbing, generally follows travel on the sea. The associated symptoms cause considerable distress. The underlying neural mechanisms are unknown, and to date there have been no effective treatments for this condition. Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied 24 subjects with persistent MdDS (3 males, 21 females; 19.1 +/- 33 months). Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test. We posited that the maladapted rocking and the physical symptoms could be diminished or extinguished by readapting the VOR. Subjects were treated by rolling the head from side-to-side while watching a rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year. Six were initially better, but the symptoms recurred. One subject did not respond to treatment. Thus, readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS. We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS, and that the symptoms can be reduced or resolved by readapting the VOR.
PMCID:4097942
PMID: 25076935
ISSN: 1664-2295
CID: 1861862

Clinical assessment of freezing of gait in Parkinson's disease from computer-generated animation

Morris, Tiffany R; Cho, Catherine; Dilda, Valentina; Shine, James M; Naismith, Sharon L; Lewis, Simon J G; Moore, Steven T
The current 'gold standard' for clinical evaluation of freezing of gait (FOG) in Parkinson's disease (PD) is determination of the number of FOG episodes from video by independent raters. We have previously described a robust technique for objective FOG assessment from lower-limb acceleration. However, there is no existing method for validation of autonomous FOG measures in the absence of video documentation. In this study we compared the results of clinical evaluation of FOG from computer-generated animations (derived from body-mounted inertial sensors) during a timed up and go test with the 'gold standard' of clinical video assessment, utilizing a cohort of 10 experienced raters from four PD centers. Agreement between the 10 clinical observers for scoring of FOG from computer animations was more robust for the relative duration of freeze events (percent time frozen; intraclass correlation coefficient of 0.65) than number of FOG episodes, and was comparable with clinical evaluation of the patient from video (intraclass correlation coefficient 0.73). This result suggests that percent time frozen should be considered (along with number of FOG events) to better convey FOG severity. The ability of clinical observers to quantify FOG from computer-generated animation derived from lower-limb motion data provides a potential approach to validation of accelerometry-based FOG identification outside of the clinic.
PMID: 23332192
ISSN: 1879-2219
CID: 4590592

Atypical Chediak-Higashi syndrome with attenuated phenotype: three adult siblings homozygous for a novel LYST deletion and with neurodegenerative disease

Weisfeld-Adams, James D; Mehta, Lakshmi; Rucker, Janet C; Dembitzer, Francine R; Szporn, Arnold; Lublin, Fred D; Introne, Wendy J; Bhambhani, Vikas; Chicka, Michael C; Cho, Catherine
BACKGROUND: Mutations in LYST, a gene encoding a putative lysosomal trafficking protein, cause Chediak-Higashi syndrome (CHS), an autosomal recessive disorder typically characterized by infantile-onset hemophagocytic syndrome and immunodeficiency, and oculocutaneous albinism. A small number of reports of rare, attenuated forms of CHS exist, with affected individuals exhibiting progressive neurodegenerative disease beginning in early adulthood with cognitive decline, parkinsonism, features of spinocerebellar degeneration, and peripheral neuropathy, as well as subtle pigmentary abnormalities and subclinical or absent immune dysfunction. METHODS: In a consanguineous Pakistani kindred with clinical phenotypes consistent with attenuated CHS, we performed SNP array-based homozygosity mapping and whole gene sequencing of LYST. RESULTS: We identified three individuals homozygous for a novel six base pair in-frame deletion in LYST (c.9827_9832ATACAA), predicting the loss of asparagine and threonine residues from the LYST transcript (p.Asn3276_Thr3277del), and segregating with the phenotype in this family. CONCLUSIONS: We further characterize the neurologic features of the attenuated form of CHS, and discuss pathophysiologic mechanisms underlying the neurodegenerative components of CHS. Attenuated CHS is phenotypically heterogenous and should be considered when young adults develop neurodegenerative disease and have pigmentary abnormalities. We briefly discuss surveillance and management of patients with CHS-related neurodegeneration.
PMCID:3610301
PMID: 23521865
ISSN: 1750-1172
CID: 1037712

Adult onset idiopathic focal lower extremity dystonia: A comparative phenomenological analysis of this novel task specific dystonia [Meeting Abstract]

Ramdhani, RA; Cho, C; Frucht, SJ
ISI:000305507703206
ISSN: 0885-3185
CID: 2785722

A comparison of clinical and objective measures of freezing of gait in Parkinson's disease

Morris, Tiffany R; Cho, Catherine; Dilda, Valentina; Shine, James M; Naismith, Sharon L; Lewis, Simon J G; Moore, Steven T
Freezing of gait, a paroxysmal motor block, is common in the latter stages of Parkinson's disease. The current 'gold standard' of assessing the severity of freezing is based on clinical identification (by up to 3 raters) of the number of episodes from video. The aims of this study were to systematically assess this 'gold standard' across multiple Parkinson's disease centers, and to compare these clinical ratings with objective measures derived from lower limb acceleration data. Video recordings were acquired during a timed up-and-go task from 10 Parkinson's disease patients (with a clinical history of freezing) in the 'off' state. Patients were instrumented with accelerometers on the lateral aspect of each shank. Ten experienced clinicians were recruited from four Parkinson's disease centers to independently assess the videos for number and duration of freezing events. The reliability of clinical video assessment for number of freezing events was moderate (intraclass correlation coefficient 0.63). Percent time frozen (cumulative duration of freezing episodes/total duration of the walking task) demonstrated stronger agreement between raters (0.73). Agreement of accelerometry-derived measures of freezing severity with mean clinician ratings was strong for number of episodes (0.78) and very strong for percent time frozen (0.93). The results demonstrate the viability of objective measures of freezing, and that percent time frozen is a more reliable metric of severity than number of freezing events for both clinical and objective measures. The large variability between clinicians suggests that caution should be used when comparing subjective ratings across centers.
PMID: 22445248
ISSN: 1873-5126
CID: 1860052

Frequency-velocity mismatch: a fundamental abnormality in parkinsonian gait

Cho, Catherine; Kunin, Mikhail; Kudo, Koji; Osaki, Yasuhiro; Olanow, C Warren; Cohen, Bernard; Raphan, Theodore
Gait dysfunction and falling are major sources of disability for patients with advanced Parkinson's disease (PD). It is presently thought that the fundamental defect is an inability to generate normal stride length. Our data suggest, however, that the basic problem in PD gait is an impaired ability to match step frequency to walking velocity. In this study, foot movements of PD and normal subjects were monitored with an OPTOTRAK motion-detection system while they walked on a treadmill at different velocities. PD subjects were also paced with auditory stimuli at different frequencies. PD gait was characterized by step frequencies that were faster and stride lengths that were shorter than those of normal controls. At low walking velocities, PD stepping had a reduced or absent terminal toe lift, which truncated swing phases, producing shortened steps. Auditory pacing was not able to normalize step frequency at these lower velocities. Peak forward toe velocities increased with walking velocity and PD subjects could initiate appropriate foot dynamics during initial phases of the swing. They could not control the foot appropriately in terminal phases, however. Increased treadmill velocity, which matched the natural PD step frequency, generated a second toe lift, normalizing step size. Levodopa increased the bandwidth of step frequencies, but was not as effective as increases in walking velocity in normalizing gait. We postulate that the inability to control step frequency and adjust swing phase dynamics to slower walking velocities are major causes for the gait impairment in PD.
PMCID:2887635
PMID: 20042701
ISSN: 1522-1598
CID: 1860042