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SPACE: An International, Non-Interventional Study of Botulinum Toxin Formulations in Treatment-Naïve Patients with Spasticity
PM&R
Poster 69 Diagnostic Challenges of Nesidioblastosis-Induced Hyperinsulinemic Hypoglycemic Peripheral Polyneuropathy: A Case Report. David Mahon, DO (Temple University Hospital, Philadelphia, PA, United States); Stephen Gingrich, MD; Ian B. Maitin, MD, MBA. Disclosures: D. Mahon, No Disclosures: I Have Nothing To Disclose. Case Description: A 51-year-old non-diabetic man presented to acute care with a one-month history of ascending weakness. He reported sensory disturbances but no neuroglycopenic symptoms. Examination revealed areflexia of the lower limbs. Neuroimaging was negative and he was treated unsuccessfully for suspected AIDP with IVIG after electrodiagnostic studies supported sensorimotor demyelinating peripheral polyneuropathy. The patient was discharged to acute inpatient rehabilitation, where he was noted to have persistent hypoglycemia. Workup was initiated and the patient improved enough functionally to return home. A month later he was readmitted with subjectively worsening weakness and was again treated unsuccessfully with IVIG for suspected relapsing AIDP. Repeat electrodiagnostic studies showed worsening polyneuropathy. The patient was found to have hyperinsulinemia and biochemical analysis indicated insulinoma, however, extensive radiological workup could not localize a tumor. Setting: Tertiary care hospital; Inpatient Acute Rehabilitation Unit; Outpatient Results or Clinical Course: The patient’s peripheral neuropathy was hypothesized to be hypoglycemic in nature, likely secondary to nesidioblastosis, as no insulinoma was found. He ultimately underwent an extended pylorus-sparing Whipple procedure, confirming nesidioblastosis by histology. Subsequently the hypoglycemia completely resolved, and the patient reported improvement in the sensory disturbances, though minimal improvement was seen in strength. Discussion: This case demonstrates potential difficulties in diagnosing peripheral polyneuropathy secondary to hyperinsulinemic hypoglycemia. Reports of insulinoma-induced hypoglycemic polyneuropathy are rare, while nesidioblastosis itself in the adult population without prior gastric surgery is even rarer. This is the first reported case, to our knowledge, of histologically proven nesidioblastosis causing polyneuropathy. Conclusions: Diagnosis of hypoglycemic neuropathy can prove challenging due to a confounding combination of signs and symptoms (or lack thereof), electrodiagnostic data, and in the case of nesidioblastosis, absence of insulin-secreting tumor. Surgical excision of pancreatic tissue may be both diagnostic and therapeutic. With treatment, functional improvements are possible, though return to baseline is guarded. Poster 70 Pseudoexacerbation of MS Secondary to Dilantin Toxicity: A Case Report. Tony K. George, DO (Tufts Medical Center, Framingham, MA, United States); Timothy Tiu, MD; Deniz Ozel, MD. Disclosures: T. K. George, No Disclosures: I Have Nothing To Disclose.
Vol. 5, Iss. 9S, 2013
S163
Case Description: This 53-year-old woman with secondary progressive MS on rituximab who was previously independent at a wheelchair level for functional mobility was admitted to acute care hospital with increasing difficulty transferring, progressive weakness greater in the upper extremities, worsening spasticity and multiple falls. Her acute hospitalization work up including full metabolic panel, CBC and urinalysis were negative for any infectious or metabolic etiology. MRI of the brain and spinal cord were negative for any new lesions. There were no recent adjustments to her ITB pump. She was on phenytoin for seizure disorder with her dose recently increased by her PCP for subtheraputic levels. Phenytoin levels were not obtained at the acute hospital. At admission to IRF, her phenytoin and albumin levels were 39.3 (N 10-20) and 3.3 (N 3.4-5.0) respectively resulting in a corrected phenytoin level of 51.7. Setting: Inpatient Rehabilitation Hospital Results or Clinical Course: Phenytoin dosing was adjusted and eventually decreased to 13.1 with a corrected phenytoin level of 17.2 at discharge. Her neurologic and functional status improved back to her baseline with these changes in addition to an interdisciplinary rehabilitation program and she was discharged home after 14 days independent for all mobility, ADLS and home management at a wheelchair level. Discussion: Medication side effects causing pseudoexacerbations of MS are common. Symptoms from phenytoin toxicity include weakness, spasticity and falls. Uncorrected phenytoin levels due to low serum albumin can mask higher toxic levels. Conclusions: In a patient with MS and underlying seizure disorder, it is important to monitor drug levels after any changes are made to the regimen due to the logarithmic curve for serum phenytoin. Furthermore, it is equally important to correct the levels for any variation in albumin as corrected levels can be much higher than non corrected levels. Poster 71 SPACE: An International, Non-Interventional Study of Botulinum Toxin Formulations in Treatment-Naïve Patients with Spasticity. Julian Harriss (King’s College Hospital, King’s College London, London, United Kingdom); Olivier Simon, MD; Nicolas Roche, MD; Carlos Cantú-Brito, MD; Svetlana E. Khatkova, MD; Patrik Säterö, MD. Disclosures: J. Harriss, No Disclosures: I Have Nothing To Disclose. Objective: To understand the long-term management of spasticity and evaluate the efficacy and safety of treatment with botulinum toxin type A in “real-life” clinical practice. Design: SPACE is a prospective, non-interventional, open-label, multi-national study. Setting: Clinical practice. Participants: Adult patients (18 years) with spasticity of any etiology or pattern who require botulinum toxin type A injections and have not been previously treated with botulinum toxin types A or B. Interventions: Patients will be followed for up to 2 years, during which time they can receive any number of treatment sessions with any botulinum toxin type A formulation available in their country. Dose (total and per muscle), dilution, injection sites, and treatment will be determined by the physician according to their usual clinical practice.
S164
Main Outcome Measures: Changes in injection intervals over time, duration and time to onset of therapeutic effect, efficacy assessments (global and focal), health-related quality of life, and tolerability. Data on treatment goals, injection technique, muscles treated, and dose used (total and per muscle) will also be collected. Results or Clinical Course: Recruitment ended in December 2012; 747 patients have been enrolled. The interim analysis set comprised 205 patients in 7 countries. The majority of patients (76.1%) had post-stroke spasticity and 83.4% were hemiplegic. Most participating physicians were neurologists. Of the 3 formulations of botulinum toxin type A commercially available in the USA and Europe, incobotulinumtoxinA (XeominÒ) was received by 83% of patients, abobotulinumtoxinA (DysportÒ) by 10% of patients, and onabotulinumtoxinA (BotoxÒ) by 7% of patients. Conclusions: Data from the SPACE study will help to further our understanding of how botulinum toxin type A is used to treat spasticity in real-life clinical practice. By identifying areas of overlap or disagreement between treatment guidelines, botulinum toxin type A product labeling and current clinical practice, data collected during this study will inform the updating of treatment guidelines and assist with designing future clinical trials. Poster 72 Paraneoplastic Syndrome Associated with Ovarian Teratoma as a Cause of Encephalitis: A Case Report. Roshni G. Durgam, MD (Albert Einstein College of Medicine / Montefiore, Bronx, NY, United States); Antigone Argyriou, MD; Michelle Stern, MD. Disclosures: R. G. Durgam, No Disclosures: I Have Nothing To Disclose. Case Description: We present a 29-year-old woman with a history of migraines and dermoid cyst who presented to the psychiatry emergency room for evaluation of visual hallucinations, aggression, and child-like behavior. She was later transferred to the medical emergency room after a witnessed tonic clonic seizure. Given her history of an ovarian cyst, anti-N-methyl-D-aspartate (NMDA) receptor antibodies were sent with positive results. Computed tomography revealed a large complex abdominopelvic mass with numerous septations containing fluid, soft tissue, and multiple calcifications consistent with a teratoma. She was diagnosed with anti-NMDA receptor encephalitis, a paraneoplastic syndrome. Setting: Tertiary care center Results or Clinical Course: Our patient underwent right salpingoophorectomy with pathology containing abundant mature brain tissue with foci of immature neural elements. Her physical exam was significant for right gaze nystagmus, psychomotor slowing, and impaired gait. Once medically optimized, she was transferred to a specialized brain injury unit, since she was not an appropriate candidate for general rehabilitation due to her agitated state. This specialized unit provided more intensive and individualized care for her cognitive decline. After a few weeks, her therapists reported marked improvement in her motor coordination and a notable regression in her psychotic outbursts. Discussion: Anti-NMDA receptor encephalitis is an entity which is difficult to diagnose since the primary symptoms are psychiatric in nature, and thus, are initially evaluated by psychiatrists.
PRESENTATIONS
Common symptoms include agitation, dyskinesias, and oculomotor impairment. The classic association is the finding of an ovarian teratoma, wherein it is proposed that the presence of immature neural tissue is related to the formation of the anti-NMDA receptor antibodies. On review of the available literature, a consistent finding is the significant improvement of symptoms with early diagnosis and teratoma removal. Prognosis is more favorable in those who receive aggressive physical rehabilitation after the acute hospitalization stage. Conclusions: Young women who present with psychiatric symptoms and have a history of ovarian pathology should be evaluated for organic causes, such as anti-NMDA receptor encephalitis. Poster 73 Preparing for Paralysis - Rehabilitation for a Rare Metastatic Meningioma: A Case Report. Sangeeta Patel, MD, MPH (Northwestern University/ Rehabilitation Institute of Chicago, Chicago, IL, United States); Gayle R. Spill, MD. Disclosures: S. Patel, No Disclosures: I Have Nothing To Disclose. Case Description: The patient is a 61-year-old man with a rare metastatic anaplastic meningioma, a malignancy with an annual incidence of 0.17 per 100,000 people. Through the continuum of this patient’s disease progression, rehabilitation interventions were instituted to improve his functional status and quality of life. Setting: Acute Care Hospital and Acute Inpatient Rehabilitation Hospital Results or Clinical Course: The patient, with known diagnosis, was initially seen by the cancer rehabilitation consult service when he was admitted with recurrent falls. An ankle-foot orthosis and walker were recommended after exam findings were notable for right dorsiflexor weakness. The patient was discharged home modified-independent with ambulation. He was re-admitted with worsening lower extremity weakness and found to have recurrence of tumor at T11 with severe cord compression. He was not a surgical candidate. He was transferred to inpatient rehabilitation knowing that he would progress to complete T11 paraplegia. As expected, he progressed to complete paraplegia within three weeks. The rehabilitation team coordinated care with Neuro-oncology and Palliative Care to maximize function and control symptoms, especially the patient’s severe anxiety. At discharge, he was modifiedindependent at the wheelchair level. Two months later, the patient was re-admitted with progressive upper extremity weakness. A day rehabilitation program was instituted for a motorized wheelchair and acquiring activities of daily living (ADL) aids such as a universal right hand cuff so he could continue to play the guitar, his passion. Due to these interventions, the patient was able to live a higher quality of life through his transition to home hospice and subsequent passing six months later. Discussion: This is an unusual case not only in its rare diagnosis but also in the way rehabilitation medicine was integrated into the patient’s care throughout his disease progression to maximize function and promote quality of life. Conclusions: This case report demonstrates how the emerging field of Cancer Rehabilitation can add value to comprehensive oncologic care even in the face of disease progression.
Poster 69 Diagnostic Challenges of Nesidioblastosis-Induced Hyperinsulinemic Hypoglycemic Peripheral Polyneuropathy: A Case Report. David Mahon, DO (Temple University Hospital, Philadelphia, PA, United States); Stephen Gingrich, MD; Ian B. Maitin, MD, MBA. Disclosures: D. Mahon, No Disclosures: I Have Nothing To Disclose. Case Description: A 51-year-old non-diabetic man presented to acute care with a one-month history of ascending weakness. He reported sensory disturbances but no neuroglycopenic symptoms. Examination revealed areflexia of the lower limbs. Neuroimaging was negative and he was treated unsuccessfully for suspected AIDP with IVIG after electrodiagnostic studies supported sensorimotor demyelinating peripheral polyneuropathy. The patient was discharged to acute inpatient rehabilitation, where he was noted to have persistent hypoglycemia. Workup was initiated and the patient improved enough functionally to return home. A month later he was readmitted with subjectively worsening weakness and was again treated unsuccessfully with IVIG for suspected relapsing AIDP. Repeat electrodiagnostic studies showed worsening polyneuropathy. The patient was found to have hyperinsulinemia and biochemical analysis indicated insulinoma, however, extensive radiological workup could not localize a tumor. Setting: Tertiary care hospital; Inpatient Acute Rehabilitation Unit; Outpatient Results or Clinical Course: The patient’s peripheral neuropathy was hypothesized to be hypoglycemic in nature, likely secondary to nesidioblastosis, as no insulinoma was found. He ultimately underwent an extended pylorus-sparing Whipple procedure, confirming nesidioblastosis by histology. Subsequently the hypoglycemia completely resolved, and the patient reported improvement in the sensory disturbances, though minimal improvement was seen in strength. Discussion: This case demonstrates potential difficulties in diagnosing peripheral polyneuropathy secondary to hyperinsulinemic hypoglycemia. Reports of insulinoma-induced hypoglycemic polyneuropathy are rare, while nesidioblastosis itself in the adult population without prior gastric surgery is even rarer. This is the first reported case, to our knowledge, of histologically proven nesidioblastosis causing polyneuropathy. Conclusions: Diagnosis of hypoglycemic neuropathy can prove challenging due to a confounding combination of signs and symptoms (or lack thereof), electrodiagnostic data, and in the case of nesidioblastosis, absence of insulin-secreting tumor. Surgical excision of pancreatic tissue may be both diagnostic and therapeutic. With treatment, functional improvements are possible, though return to baseline is guarded. Poster 70 Pseudoexacerbation of MS Secondary to Dilantin Toxicity: A Case Report. Tony K. George, DO (Tufts Medical Center, Framingham, MA, United States); Timothy Tiu, MD; Deniz Ozel, MD. Disclosures: T. K. George, No Disclosures: I Have Nothing To Disclose.
Vol. 5, Iss. 9S, 2013
S163
Case Description: This 53-year-old woman with secondary progressive MS on rituximab who was previously independent at a wheelchair level for functional mobility was admitted to acute care hospital with increasing difficulty transferring, progressive weakness greater in the upper extremities, worsening spasticity and multiple falls. Her acute hospitalization work up including full metabolic panel, CBC and urinalysis were negative for any infectious or metabolic etiology. MRI of the brain and spinal cord were negative for any new lesions. There were no recent adjustments to her ITB pump. She was on phenytoin for seizure disorder with her dose recently increased by her PCP for subtheraputic levels. Phenytoin levels were not obtained at the acute hospital. At admission to IRF, her phenytoin and albumin levels were 39.3 (N 10-20) and 3.3 (N 3.4-5.0) respectively resulting in a corrected phenytoin level of 51.7. Setting: Inpatient Rehabilitation Hospital Results or Clinical Course: Phenytoin dosing was adjusted and eventually decreased to 13.1 with a corrected phenytoin level of 17.2 at discharge. Her neurologic and functional status improved back to her baseline with these changes in addition to an interdisciplinary rehabilitation program and she was discharged home after 14 days independent for all mobility, ADLS and home management at a wheelchair level. Discussion: Medication side effects causing pseudoexacerbations of MS are common. Symptoms from phenytoin toxicity include weakness, spasticity and falls. Uncorrected phenytoin levels due to low serum albumin can mask higher toxic levels. Conclusions: In a patient with MS and underlying seizure disorder, it is important to monitor drug levels after any changes are made to the regimen due to the logarithmic curve for serum phenytoin. Furthermore, it is equally important to correct the levels for any variation in albumin as corrected levels can be much higher than non corrected levels. Poster 71 SPACE: An International, Non-Interventional Study of Botulinum Toxin Formulations in Treatment-Naïve Patients with Spasticity. Julian Harriss (King’s College Hospital, King’s College London, London, United Kingdom); Olivier Simon, MD; Nicolas Roche, MD; Carlos Cantú-Brito, MD; Svetlana E. Khatkova, MD; Patrik Säterö, MD. Disclosures: J. Harriss, No Disclosures: I Have Nothing To Disclose. Objective: To understand the long-term management of spasticity and evaluate the efficacy and safety of treatment with botulinum toxin type A in “real-life” clinical practice. Design: SPACE is a prospective, non-interventional, open-label, multi-national study. Setting: Clinical practice. Participants: Adult patients (18 years) with spasticity of any etiology or pattern who require botulinum toxin type A injections and have not been previously treated with botulinum toxin types A or B. Interventions: Patients will be followed for up to 2 years, during which time they can receive any number of treatment sessions with any botulinum toxin type A formulation available in their country. Dose (total and per muscle), dilution, injection sites, and treatment will be determined by the physician according to their usual clinical practice.
S164
Main Outcome Measures: Changes in injection intervals over time, duration and time to onset of therapeutic effect, efficacy assessments (global and focal), health-related quality of life, and tolerability. Data on treatment goals, injection technique, muscles treated, and dose used (total and per muscle) will also be collected. Results or Clinical Course: Recruitment ended in December 2012; 747 patients have been enrolled. The interim analysis set comprised 205 patients in 7 countries. The majority of patients (76.1%) had post-stroke spasticity and 83.4% were hemiplegic. Most participating physicians were neurologists. Of the 3 formulations of botulinum toxin type A commercially available in the USA and Europe, incobotulinumtoxinA (XeominÒ) was received by 83% of patients, abobotulinumtoxinA (DysportÒ) by 10% of patients, and onabotulinumtoxinA (BotoxÒ) by 7% of patients. Conclusions: Data from the SPACE study will help to further our understanding of how botulinum toxin type A is used to treat spasticity in real-life clinical practice. By identifying areas of overlap or disagreement between treatment guidelines, botulinum toxin type A product labeling and current clinical practice, data collected during this study will inform the updating of treatment guidelines and assist with designing future clinical trials. Poster 72 Paraneoplastic Syndrome Associated with Ovarian Teratoma as a Cause of Encephalitis: A Case Report. Roshni G. Durgam, MD (Albert Einstein College of Medicine / Montefiore, Bronx, NY, United States); Antigone Argyriou, MD; Michelle Stern, MD. Disclosures: R. G. Durgam, No Disclosures: I Have Nothing To Disclose. Case Description: We present a 29-year-old woman with a history of migraines and dermoid cyst who presented to the psychiatry emergency room for evaluation of visual hallucinations, aggression, and child-like behavior. She was later transferred to the medical emergency room after a witnessed tonic clonic seizure. Given her history of an ovarian cyst, anti-N-methyl-D-aspartate (NMDA) receptor antibodies were sent with positive results. Computed tomography revealed a large complex abdominopelvic mass with numerous septations containing fluid, soft tissue, and multiple calcifications consistent with a teratoma. She was diagnosed with anti-NMDA receptor encephalitis, a paraneoplastic syndrome. Setting: Tertiary care center Results or Clinical Course: Our patient underwent right salpingoophorectomy with pathology containing abundant mature brain tissue with foci of immature neural elements. Her physical exam was significant for right gaze nystagmus, psychomotor slowing, and impaired gait. Once medically optimized, she was transferred to a specialized brain injury unit, since she was not an appropriate candidate for general rehabilitation due to her agitated state. This specialized unit provided more intensive and individualized care for her cognitive decline. After a few weeks, her therapists reported marked improvement in her motor coordination and a notable regression in her psychotic outbursts. Discussion: Anti-NMDA receptor encephalitis is an entity which is difficult to diagnose since the primary symptoms are psychiatric in nature, and thus, are initially evaluated by psychiatrists.
PRESENTATIONS
Common symptoms include agitation, dyskinesias, and oculomotor impairment. The classic association is the finding of an ovarian teratoma, wherein it is proposed that the presence of immature neural tissue is related to the formation of the anti-NMDA receptor antibodies. On review of the available literature, a consistent finding is the significant improvement of symptoms with early diagnosis and teratoma removal. Prognosis is more favorable in those who receive aggressive physical rehabilitation after the acute hospitalization stage. Conclusions: Young women who present with psychiatric symptoms and have a history of ovarian pathology should be evaluated for organic causes, such as anti-NMDA receptor encephalitis. Poster 73 Preparing for Paralysis - Rehabilitation for a Rare Metastatic Meningioma: A Case Report. Sangeeta Patel, MD, MPH (Northwestern University/ Rehabilitation Institute of Chicago, Chicago, IL, United States); Gayle R. Spill, MD. Disclosures: S. Patel, No Disclosures: I Have Nothing To Disclose. Case Description: The patient is a 61-year-old man with a rare metastatic anaplastic meningioma, a malignancy with an annual incidence of 0.17 per 100,000 people. Through the continuum of this patient’s disease progression, rehabilitation interventions were instituted to improve his functional status and quality of life. Setting: Acute Care Hospital and Acute Inpatient Rehabilitation Hospital Results or Clinical Course: The patient, with known diagnosis, was initially seen by the cancer rehabilitation consult service when he was admitted with recurrent falls. An ankle-foot orthosis and walker were recommended after exam findings were notable for right dorsiflexor weakness. The patient was discharged home modified-independent with ambulation. He was re-admitted with worsening lower extremity weakness and found to have recurrence of tumor at T11 with severe cord compression. He was not a surgical candidate. He was transferred to inpatient rehabilitation knowing that he would progress to complete T11 paraplegia. As expected, he progressed to complete paraplegia within three weeks. The rehabilitation team coordinated care with Neuro-oncology and Palliative Care to maximize function and control symptoms, especially the patient’s severe anxiety. At discharge, he was modifiedindependent at the wheelchair level. Two months later, the patient was re-admitted with progressive upper extremity weakness. A day rehabilitation program was instituted for a motorized wheelchair and acquiring activities of daily living (ADL) aids such as a universal right hand cuff so he could continue to play the guitar, his passion. Due to these interventions, the patient was able to live a higher quality of life through his transition to home hospice and subsequent passing six months later. Discussion: This is an unusual case not only in its rare diagnosis but also in the way rehabilitation medicine was integrated into the patient’s care throughout his disease progression to maximize function and promote quality of life. Conclusions: This case report demonstrates how the emerging field of Cancer Rehabilitation can add value to comprehensive oncologic care even in the face of disease progression.