UCLA Medical Record 4/2023
Don Sladek's journey with CBS and his improvement with Gosuranemab
DATE OF SERVICE:
I had the pleasure of seeing Mr. Sladek in the Movement Disorders Clinic UCLA Medical Center for followup of corticobasal syndrome. His wife accompanied him to this visit.
HISTORY OF PRESENT ILLNESS:
Mr. Sladek is a 69-year-old, left-handed gentleman with an approximate 8-year history of likely corticobasal degeneration with the onset of right-sided dystonia and myoclonus accompanied by gait and balance impairment. In the past, he completed the Tau-Basket trial at UCSF with notable improvement in cognitive and motor symptoms with monthly infusions of gosuranemab. Prior to this clinical trial, he had had continued progression of corticobasal syndrome-type symptoms, specifically rigidity, dystonia, myoclonus, gait imbalance impairment, speech impairment, despite medication optimization. Prior to the clinical trial, he was being referred for swallowing assessments, given the advanced dysphagia, as well as speech therapy for speech impairment. He was using assist devices to ambulate safely and was also being referred for more intensive physical therapy for the gait and balance deterioration. Given the disease progress, we had also recommended a referral to the palliative care team. However, during his participation in the clinical trial of gosuranemab, where he received monthly infusions, there was gradual improvement and stabilization of symptoms. The clinical trial was terminated in December 2019, due to lack of efficacy in a different clinical trial of the same drug in subjects with PSP. He experienced gradual worsening of symptoms throughout 2020, until he received approval to proceed with monthly gosuranemab infusions during single-patient expanded use access in conjunction with Biogen. Since restarting this therapy, his neurologic symptoms have once again improved and have remained quite stable through the course of his treatment. He no longer requires a cane for ambulation, and we have not moved forward with palliative care assessments. He is followed on a monthly basis just prior to his infusions, and was seen 1 month ago in March for his 33rd infusion. He tolerated that infusion well, as he has all other past infusions. Monthly chemistry panels and CBCs have been essentially within normal limits, today's include. Since his last visit in March, he has had some intermittent worsening of symptoms. This is related to usually intense physical and emotional stressors. There was 1 day in particular where he had an episode described as an onset of generalized weakness and lack of responsivity. He did not lose consciousness and did not have any lightheadness prior to or during the episode. It was late in the evening prior to his bedtime dose of medications. There were no abnormal movements suggestive of seizure-type activity and no exacerbation of dystonia, which has happened in the past where he had 1 to 2 days of significant exacerbation of dystonia, similar to a dystonic storm type of reaction. This was more weakness. He slept through the night and actually slept most of the next day and eventually got back into his usual routine and recovery and did not have a similar episode since. He has had no falls. He has been exercising regularly otherwise.
PAST MEDICAL HISTORY:
He had excision of another skin cancer on his right cheek. No new medical problems otherwise.
No known drug allergies.
These medications have been stable prior to and during his treatment with gosuranemab, and thus all benefits in symptoms control are likely attributed to the monthly gosuranemab infusions. His symptomatic medications include Sinemet 25/250 one tablet q.i.d. at 7 a.m., 11 a.m., 5 p.m., and midnight, entacapone 200 mg with each dose of Sinemet, clonazepam 0.5 mg tablets 1 tablet at 3 p.m., 3 tablets q.h.s., levetiracetam 1000 mg t.i.d., sertraline 200 mg daily, gabapentin 300 mg capsules 3 capsules q.i.d., Synthroid, dexlansoprazole, and Lipitor.
SOCIAL HISTORY AND FAMILY HISTORY:
Remain unchanged. He continues to establish care within the VA system, given his toxic exposures while in Vietnam (should be exposures in Thailand during the Vietnam war). Family history is significant for a brother, Scott, who has a phenotype of tremor-dominant Parkinson's disease with the age of onset at 59. His brother, Tom, had exposures while working as a contractor in Iraq during the Iraq War, where he incurred traumatic brain injury, as well as being exposed to toxins from the burn pits, and had at least 8 concussions in total during his lifetime. He has had the onset of a frontotemporal dementia type phenotype at the age of 62. His father had the onset of dementia at 90 and is currently in a nursing home, and is currently 93 years old.
MOVEMENT DISORDERS EXAMINATION:
Blood pressure was 125/61, and pulse was 78. He was afebrile, and his weight was 288 pounds. He was examined 3 hours after his last dose of medications. Eye movements were full range. There were no square wave jerks. Ocular pursuit was mildly interrupted. Myerson's sign was absent, but there was diminished blink rate. There was no significant hypomimia, but there was mild hypophonia and speech hesitation, more so than at past visits. There were no paraphasic errors. Tone was normal in his neck and all 4 extremities at today's visit. No myoclonus was observed at today's visit. There were no rest, posture, or kinetic tremors. There was mild overall bradykinesia and mild bradykinesia of hand and foot movements bilaterally. There was mild to moderate ideomotor and mild ideational apraxia of both hands, worse on the right. Applause sign was absent. He rose from a chair without support of his arms, but did so slowly. His posture was quite good. His gait was remarkable for being slow and mildly unsteady at today's visit and mildly wide based. He was able to tandem without deviation, but did so very slowly. He recovered independently on the pull test. There was no freezing of gait.
ASSESSMENT AND PLAN:
Mr. Sladek is a 69-year-old, left-handed gentleman with an approximate 8-year history of likely corticobasal syndrome most consistent with corticobasal degeneration with the onset of rigidity, bradykinesia, dystonia, myoclonus, and apraxia. There is a familial component, now with 2 of his brother is exhibiting neurodegenerative disease symptoms, and his father being the only additional family member with onset of dementia at an older age in his 90s.
He has participated in multiple studies and clinical trials, but genetic testing results have not been made available. Therefore, we will send off the Invitae panel to assess for any known variants in gene mutations related to the frontotemporal dementia type syndromes, including C9orf72. This is an effort not only to better understand his underlying diagnosis, but to help explain the response that he has had to the tau antibody therapies.
He has achieved significant improvement in motor, behavioral and cognitive symptoms, first while participating in the gosuranemab trial in 2019 at UCSF, and now with expanded use access, having completed 33 infusions thus far. This therapy continues to provide meaningful benefit.
Of note, his PSP rating scale prior to initiation of his therapy here was 39, and his Schwab and England independent functioning score was 70%. His PSP rating scale today was 12, and his Schwab and England score is 95%. This documents objective improvement in motor symptoms and stability of these motor symptoms over the course of his treatment with monthly infusions. He has also noted subjective improvement in overall mobility, behavioral, and cognitive function as well as quality of life.
Symptomatic therapy will remain the same as it has throughout the course of his treatment with this investigational therapy, including levodopa, entacapone, levetiracetam, clonazepam, sertraline and gabapentin. He will also continue with his active exercise regimen, which has also been beneficial.
He will continue with monthly infusions of gosuranemab, starting his 34th infusion later today and in 1 month's time for his next infusion until the supply runs out. We have only been provided with a limited number of treatments from Biogen. In the meantime, he will be in touch with any questions or concerns.
Total encounter time including chart review, face-to-face visit, documentation, counseling, and coordination of care 40 minutes.
Yvette M. Bordelon MD, MD, PhD (P23533)
YMB/MODL CONF#: 194148
D: 04/18/2023 10:54:10 T: 04/19/2023 00:41:37 DOCUMENT: 990567102