Accepted Manuscript Rehabilitation of the Pontine Ataxia-Dysmetria Syndrome: A Case Presentation Stephanie Li, MD, Kasondra Hartman, BS, Krishna Surapaneni, MD, Eric L. Altschuler, MD, PhD PII: S1934-1482(17)30028-X DOI: 10.1016/j.pmrj.2017.01.001 Reference: PMRJ 1837 To appear in: PM&R Received Date: 6 September 2016 Revised Date: 3 January 2017 Accepted Date: 8 January 2017 Please cite this article as: Li S, Hartman K, Surapaneni K, Altschuler EL, Rehabilitation of the Pontine Ataxia-Dysmetria Syndrome: A Case Presentation, PM&R (2017), doi: 10.1016/j.pmrj.2017.01.001. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ACCEPTED MANUSCRIPT Case Presentation: RI PT Rehabilitation of the Pontine Ataxia-Dysmetria Syndrome SC Stephanie Li1, MD, Kasondra Hartman2, BS, Krishna Surapaneni3, MD, Eric L Altschuler1*, MD, PhD 1 M AN U Department of Physical Medicine and Rehabilitation, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA 2 The Commonwealth Medical College, Scranton, PA, USA 3 Department of Radiology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA AC C EP TE D *To whom correspondence should be addressed: Eric L Altschuler, MD, PhD 3401 North Broad Street Philadelphia, PA 19140, USA email: eric.altschuler@temple.edu Phone: (215) 707-7021 Fax: (215) 707-9168 KH was partially supported by a grant from the Craig H. Nielson Foundation through a RREMS Fellowship from the Association of Academic Physiatrists. We have no financial or other conflicts. ACCEPTED MANUSCRIPT 1 2 Rehabilitation of the Pontine Ataxia-Dysmetria Syndrome: A Case Presentation 3 5 RI PT 4 We have no financial or other conflicts. 6 7 AC C EP TE D M AN U SC 8 ACCEPTED MANUSCRIPT Abstract 10 11 12 13 14 15 16 17 18 We present a case of a patient with significant ataxia and dysmetria following a lacunar pontine infarction and review the literature on this uncommon syndrome. The patient had an excellent clinical course with near resolution of symptoms and signs in less than three weeks. We characterize and illustrate with videos of the ataxia and dysmetria. Interestingly, the characteristics of the dysmetria appear to be different than that seen in patients with dysmetria arising from a cerebellar or thalamic lesion. We discuss the likely neurophysiologic mechanisms responsible for the condition and recovery. Simple non-invasive study of patients with ataxia and dysmetria secondary to a pontine lacunar infarct may be most helpful in elucidating the contribution of pontocerebellar fibers to motor control. SC RI PT 9 AC C EP TE D M AN U 19 ACCEPTED MANUSCRIPT RI PT Introduction The clinical finding of ataxia is commonly seen in patients with cerebellar lesions, but is certainly not pathognomonic for cerebellar damage. It can also be seen with lesions in other brain structures such as the thalamus [1-7]. In the 1980s and 1990s, several authors described a syndrome of ataxia and dysmetria associated with a thalamic lesion [1-6]. Dysmetria, a Greek term for "wrong length," is a clinical sign that expresses the inability to alternatively touch another person's fingertip with one's own fingertip and then touch the tip of one's own nose. Interestingly, while patients with the thalamic ataxia-dysmetria syndrome are not typically paretic, they usually present with impaired gait. These patients tend to fully recover rather quickly, thus, their rehabilitation requirements differ from a more typical patient with hemiparesis following stroke. M AN U SC The following case report is of a patient admitted to acute inpatient rehabilitation (AIR) with severe ataxia, moderate dysmetria, and poor gait following a stroke involving the pons. Interestingly, the dysmetria was qualitatively different than that of classic cerebellar or thalamic dysmetria [7]. Here, we describe the clinical presentation and rehabilitation course of this patient. EP TE D Case Presentation A 63-year-old female presented to the emergency department with sudden onset slurred speech, poor balance, and left-sided weakness. The patient's prior medical history included diabetes and hypertension. Her blood pressure was 195/90 and blood sugar was 290. The initial emergency department examination noted mild left upper and lower extremity weakness, mild dysarthria, and significant left arm dysmetria and ataxia. A brain magnetic resonance imaging (MRI) study revealed an acute ischemic lacunar infarct in the right hemi-pons (Figure 1). One day following admission, she was able to ambulate 20-25 feet with a rolling walker and 50% assistance (minimum to moderate) from a physical therapist, but with poor balance. She was admitted to AIR four days later with the following examination findings: mild weakness in the left upper and lower extremities, significant dysmetria with the left hand (see supplemental Video 1-taken on first day of AIR), mild hyperreflexia in the left upper extremity, no dysarthria, normal cranial nerve function, normal sensation in all limbs, and normal right-sided strength. The patient's gait was significantly ataxic with increased swaying of the trunk and loss of balance posteriorly (see supplemental Video 2-taken on second day of AIR). Functional status at admission to AIR was the following: required moderate assistance for sit-to-stand transfers; minimal assist for ambulation 30 to 50 feet with a rolling walker; minimum to moderate assistance for lower body dressing, bed transfers, and showering; and minimum assistance with toileting. During occupational therapy, her only complaint was some fatigue with left upper extremity activities. AC C 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 She made significant gains in therapy and was discharged after two weeks at a modified independence level for sit-to-stand transfers. She could ambulate a distance of 150ft, two times, with the assistance of a rolling walker. Strength on the left side was normal at discharge, and the dysmetria and ataxia had improved significantly (see supplemental videos 3 and 4). Gait demonstrated decreased cadence, but normal base of support and improved truncal ataxia. The patient was independent for other activities of daily living, except modified independence for bathing. ACCEPTED MANUSCRIPT When seen at follow-up three weeks after discharge from acute rehabilitation, the patient was doing extremely well and had had no falls. She was able to walk long distances without an assistive device, but she turned around slowly. Her examination revealed a trace of dysmetria in the left arm. RI PT Discussion SC We describe the presentation and rehabilitation course of a patient with ataxia and dysmetria secondary to a pontine lesion. The syndrome is remarkable for severe ataxia, gait dysfunction and dysmetria without paresis or sensory loss, typically followed by a full rapid recovery. This course is similar to patients with ataxia and dysmetria following thalamic stroke [1-7]. In contradistinction, patients with hemiparesis following stroke may not have such a good or rapid recovery. M AN U More than 50 years ago [8, 9], Fisher and Cole [9] hypothesized that weakness contralateral to a stroke lesion resulted from disruption of corticospinal fibers, while contralateral dysmetria was secondary to damage to neurons in the pons or their axons. Using isotope tract tracing in rhesus monkeys, Schmahmann and colleagues [10] demonstrated that a lesion to decussating pontocerebellar fibers caused contralateral dysmetria. They suggest [10] that unmasking of redundant or reorganization of pontocerebellar fibers is responsible for the rapid clinical recovery EP TE D The dysmetria seen in our patient is not the classic cerebellar dysmetria [11]. Indeed, patients with cerebellar dysmetria do not successfully attain the target. Cerebellar patients typically start off with the wrong target and over or under correct but still typically miss the target. Our patient was able to successfully attain the target. Therefore, one might say pontine dysmetria is technically a bit of a misnomer. The dysmetria seen in a patient with a pontine lesion also differs from the dysmetria recently characterized in a patient with a thalamic lesion [7]. The patient with dysmetria secondary to a thalamic lesion initially moves slowly to the target, but distally “online guidance” of the hand appears to fail and the patient has to make corrections to attain the target. In our patient, guidance of the hand fails much more proximally nearly at the beginning of the reaching process and continues throughout, necessitating corrections through the reaching process in order to maintain a relatively straight “average” reaching trajectory in route to successfully attaining the target. Worthy of further assessment is the nature and extent of differences in the ataxia and gait dysfunction in the patient with pontine vs. thalamic ataxia. AC C 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 With the current patient, the dysmetric limb was her non-dominant arm and her main symptomatic complaint was fatigue during upper extremity specific tasks. In patients whose dominant side is affected, they may be more disabled and symptomatic. For example, while trying to drink a cup of coffee, the patient might start the tilt too early, leading to spills; perhaps, the use of a cup with a straw might be a helpful accommodation in such a situation. ACCEPTED MANUSCRIPT RI PT In larger formal studies on the rehabilitation course of patients with the pontine and thalamic ataxia-dysmetria syndromes it would be interesting to determine what percentage of patients may not have a good clinical recovery. Our case seems a human analogue of the studies in monkeys of Schmahmann and colleagues [10]. It would also be interesting and important to understand the neurophysiologic mechanism or substrate of improvement of ataxia-dysmetria in patients who have had a thalamic stroke. Improvements in imaging and data analysis technology may allow study of this dynamic in animal models. M AN U SC Finally, during the time when these patients are symptomatic with dysmetria and ataxia, there is an outstanding opportunity to learn about the contribution of pontocerebellar fibers and the thalamus to motor control in humans. Formal quantitative study of reaching in these patients comparing the trajectory of the affected arm to the unimpaired arm as a control should help delineate the contribution of the lesioned structure (e.g., pontocerebeallar fibers or thalamus) to motor control. Similarly, though more difficult, the contribution of these brain structures to control of gait can be studied with formal gait analysis. The humble finger-nose-finger test may prove to be a remarkably useful paradigm to reveal the function of deep brain structures in motor control. Key: Figure 1: Fluid-attenuated inversion recovery (FLAIR) axial MRI image demonstrates increased signal in the right medial pons at the site of an acute lacunar infarct. References TE D Video 1: Left hand dysmetria (day 1 of acute rehabilitation). Video 2: Ataxic gait (day 2 of acute rehabilitation). Video 3: Left hand dysmetria greatly improved at time of discharge. Video 4: Gait greatly improved at time of discharge. EP 1. 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Confin Neurol. (Basel) 1964; 24:37-61. AC C 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 ACCEPTED MANUSCRIPT EP TE D M AN U SC RI PT 9. Fisher CM, Cole M. Homolateral ataxia and crural paresis: a vascular syndrome. J Neurol Neurosurg Psychiatry 1965; 28: 48–55. 10. Schmahmann JD, Rosene DL, Pandya DN. Ataxia after pontine stroke: insights from pontocerebellar fibers in monkey. Ann Neurol. 2004; 55: 585-9. 11. Bodranghien F, Bastian A, Casali C, et al. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome. Cerebellum. 2016; 15: 369-391. AC C 157 158 159 160 161 162 M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D Figure 1: Fluid-attenuated inversion recovery (FLAIR) axial MRI image demonstrates increased signal in the right medial pons at the site of an acute lacunar infarct.