Pathologically Confirmed Alzheimer's Disease Presenting as Clinical Parkinson's Disease, A Case Report.

BACKGROUND: It is well known that rare cases of Alzheimer's disease (AD) pathology may cause corticobasal or posterior cortical atrophy syndromes, and that cases with advanced AD may develop parkinsonism. However, reports of parkinsonism as an initial manifestation of AD have rarely been documented. OBJECTIVES: To demonstrate that a syndrome meeting all criteria for a clinical diagnosis of idiopathic Parkinson's disease (PD) may be an initial and years-long sustained manifestation of pathologically confirmed AD. METHODS: Clinico-pathological case. RESULTS: We present a case with a 12-year clinical presentation consistent with a typical course of idiopathic Parkinson's disease, including dementia developing 6 years after the PD diagnosis. The patient improved, but only mildly, to standard treatment for PD motor symptoms. The neuropathological examination identified AD changes, and no evidence to support a concomitant diagnosis of PD. CONCLUSIONS: The absence of alpha-synucleinopathy, coupled with the patient's dementia history and AD changes in neuropathological examination, indicated the diagnosis of AD and no supplementary explanation. Neuronal loss with neurofibrillary tangles and amyloid plaques in the brainstem, substantia nigra, and locus coeruleus likely contributed to Parkinsonism features.

In early Parkinson disease, daily subcutaneous lixisenatide reduced motor disability progression at 12 mo.

SOURCE CITATION: Meissner WG, Remy P, Giordana C, et al; LIXIPARK Study Group. Trial of lixisenatide in early Parkinson's disease. N Engl J Med. 2024;390:1176-1185. 38598572.

Autopsy-Proven "Pure" Parkinson's Disease with Rapidly Progressive Dementia and Cognitive Fluctuations in a Patient with GBA Mutation.

BACKGROUND: Parkinson's disease (PD) progresses at highly variable rates in different individuals but, in general, has a fairly stable rate of progression in each patient. In cases where the decline in cognition and behavior suddenly accelerates, we usually think of co-existent Alzheimer pathology, as most demented PD patients also have Alzheimer disease (AD) changes, although not necessarily meeting criteria for a distinct pathological diagnosis of AD. METHODS: Clinico-pathological case Results: A 75-year-old woman presented with a typical PD course including a good response to L-Dopa. Four years after diagnosis she developed a rapid decline in motor symptoms, severe cognitive fluctuations, and rapidly progressive dementia, dying within one year of the onset of the rapid progression. CONCLUSIONS: While most cases of Parkinson's disease dementia (PDD) show concomitant Alzheimer's pathology, the sudden acceleration of the disease does not necessarily indicate the presence of concomitant Alzheimer's disease.

Isolated Toe Tremor Associated with Antiphospholipid Syndrome.

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies and related disorders, generally thromboses, miscarriages, livedo reticularis or heart valve abnormalities. It is thought to have a prevalence of about 40-50 cases per 100,000 in the general population.1 Several neurological disorders have been associated with APS, most commonly stroke, but non-stroke complications, thought due to auto- immune problems, have been noted, with chorea being the most common. Isolated toe tremor, that is, without any other neurological signs or symptoms, has not been reported. We describe a case of recurrent isolated uni- lateral toe tremor in an otherwise healthy woman with long-standing APS.

Parkinson's disease psychosis management: an evidence based, experience informed, pragmatic approach.

INTRODUCTION: Psychotic symptoms in people with Parkinson's disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of 'minor' hallucinations. AREAS COVERED: This article focuses both on the phenomenology of psychotic symptoms and their management. EXPERT OPINION: Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches.

Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. 'Minor hallucinations' rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail.

The Clinician's Tardive Inventory (CTI): A New Clinical Tool for Documenting and Rating Tardive Dyskinesia.

Objective: Current clinician-rated tardive dyskinesia (TD) symptom scales have not addressed the expanding clinical signs and functional impact of TD. The study objective was to develop and test the reliability of a new integrated instrument.Methods: A movement disorder neurologist devised the outline of the rating scale. A Steering Committee (5 neurologists and 2 psychiatrists) provided revisions until consensus was reached. The Clinician's Tardive Inventory (CTI) assesses abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, and limb/trunk; complex movements defined as complicated movements different from simple patterned movements or postures; and vocalizations. The CTI rates frequency of symptoms from 0 to 3 (ranging from absent to constant). Functional impairments, including activities of daily living (ADL), social impairment, symptom distress, and physical harm, are rated 0-3 (ranging from unawareness to severe impact). The CTI underwent interrater and test-retest reliability testing between February and June 2022 based on videos and accompanying vignettes, which were reviewed by 2 movement disorder specialists to determine adequacy. Four clinicians rated each video/vignette. Interrater agreement was analyzed via 2-way random-effects intraclass correlation (ICC), and test-retest agreement was assessed utilizing the Kendall tau-b.Results: Forty-five video/vignettes were assessed for interrater reliability and 16 for test-retest reliability. The most prevalent movements were those of the tongue and mouth (77.8%) and jaw (55.6%). ICCs for movement frequency for anatomic symptoms were as follows: anatomic symptom summary score 0.92, abnormal eye movement 0.89, abnormal tongue/mouth movement 0.91, abnormal jaw movement 0.89, abnormal limb movement 0.76, complex movement 0.87, and abnormal vocalization 0.77; ICCs for functional impairments were as follows: total impairment score 0.92, physical harm 0.82, social embarrassment 0.88, ADLs 0.83, and symptom bother 0.92; Retests were conducted a mean (SD) of 15 (3) days later with correlation coefficients ranging from 0.66 to 0.87.Conclusions: The CTI is a new integrated instrument with proven reliability in assessing TD signs and functional impacts. Future validation study is warranted.

Brief commentary: Under-recognition of underuse of clozapine in treating psychotic symptoms in Parkinson's disease.

Clozapine is an important drug in the treatment of Parkinson's disease (PD). It has proven efficacy in treating PD psychosis without worsening motor function, as well as in treating tremor refractory to L-Dopa, yet it is severely underused in the United States. Unlike the situation of treatment resistant schizophrenia, this underuse is underrecognized.

Amantadine for Refractory Tremor in Parkinson Disease and Other Indications: A Chart Review With Long-Term Follow-up.

OBJECTIVES: The aim of this study was to determine how amantadine was used in a movement disorders clinic and how effective it was. METHODS: A chart review over a 2-month period in 2022 of all patients in a movement disorders clinic who had ever taken amantadine was undertaken. RESULTS: One hundred six charts were included. Amantadine was initiated primarily for tremor and secondly for l -dopa-induced dyskinesias (LIDs). Sixty-two percent of tremor patients improved and tolerated amantadine; 74% of those with LID improved and tolerated the drug. Hallucinations occurred in 23%. Initiating amantadine as a syrup allowed a more conservative titration than other formulations, which is attractive given the high percentage of hallucinations that may occur. Patients who tolerated drug initiation were generally kept on the drug for many years. CONCLUSIONS: Amantadine should be considered as adjunctive therapy in Parkinson disease patients with refractory tremor as well as for LIDs.

Dopamine Transporter Scan (DAT) in Parkinsonism - a Short Review for Non-Neurologists.

The Dopamine Transporter Scan (DaT) is a radionuclear imaging technique which was approved by the FDA to differentiate essential tremor (ET) from Parkinson's disease (PD). The scan is a crude indicator of the number of dopamine-secreting cells and is abnormal in presynaptic parkinsonian syndromes. In this article we review this and other possible clinical situations in which a DaT scan may be useful.