Idiopathic Late-onset Cerebellar Ataxia Research Articles

Magnetic Resonance Imaging Marker for the Conversion from Idiopathic Late-onset Cerebellar Ataxia to Multiple System Atrophy

Magnetic Resonance Imaging Marker for the Conversion from Idiopathic Late-onset Cerebellar Ataxia to Multiple System Atrophy

Deep phenotyping in ataxia: The Massachusetts General Hospital (MGH) Ataxia Center: A three-decade retrospective (P9-11.007)

<h3>Objective:</h3> We reviewed the ~3-decade experience of the MGH Ataxia Center to identify the diagnoses in patients presenting with ataxia, and to determine the success rate of diagnosis. <h3>Background:</h3> Exponential increase in the range of diagnoses in patients with cerebellar ataxia represents a challenge to the clinician. Genetic testing facilitated this advance and heightened the need for meticulous phenotyping to determine who needs gene testing, and which results are meaningful. <h3>Design/Methods:</h3> Our Patient List is an IRB-approved ongoing catalog of patients seen in the MGH Ataxia Center since its establishment in 1994, including patients followed by the Principal Investigator since 1989. We reviewed medical records of each patient: clinical evaluations, pertinent imaging, and laboratory data. When indicated we contacted gene testing labs to update information, and in some we sought re-evaluation of gene data or autopsy findings because of new genetic developments. <h3>Results:</h3> The Patient List includes 1,690 Ataxia Center patients. The diagnoses were “non-genetic” in 969, “genetic” in 679, and ongoing workup or lost to follow-up in 42. Non-genetic included acquired and degenerative cerebellar disorders such as multiple system atrophy, and non-cerebellar disorders with a gait impairment, such as normal pressure hydrocephalus and functional neurological disorder. Genetic cases were categorized as molecularly confirmed, molecularly probable, candidate diagnosis, negative work-up with genetic tests available at the time, inconclusive, or at-risk due to positive family history. Idiopathic late onset cerebellar ataxia was designated only after exhaustive negative investigation including exome analysis. Using the clinically driven method the diagnostic success was 85.5 % for all patients, and 70.8% in those with clinically suspected genetic diagnoses. <h3>Conclusions:</h3> Diagnostic success in the MGH Ataxia Center provides support for the precision medicine approach of deep clinical phenotyping as the precursor to targeted testing and underscores the need for specialized expertise in Ataxia Centers of Excellence. <b>Disclosure:</b> The institution of Dr. Crotty has received research support from Parkinson’s Foundation. Ms. Chen has nothing to disclose. Ms. Mize has nothing to disclose. Dr. Gupta has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Biogen. The institution of Dr. Gupta has received research support from Biogen. Dr. Stephen has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SwanBio Therapeutics. The institution of Dr. Stephen has received research support from Sanofi. Dr. Stephen has received research support from National Institutes of Health. Jason MacMore has nothing to disclose. Dr. Schmahmann has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medavante. Dr. Schmahmann has stock in Cadent. The institution of Dr. Schmahmann has received research support from National Ataxia Foundation. The institution of Dr. Schmahmann has received research support from Biohaven. Dr. Schmahmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care. Dr. Schmahmann has received publishing royalties from a publication relating to health care.

Rapidly Progressive Cerebellar Ataxia and Dementia due to Cortical Cerebellar and Thalamic Degeneration: A Case Series of Two Autopsy Confirmed Patients (P8-11.016)

<h3>Objective:</h3> To report two patients with sporadic, adult-onset ataxia with a rapidly progressive disease course and extra-cerebellar symptoms resembling prion disease. <h3>Background:</h3> Sporadic, adult-onset cerebellar ataxia is a disease with multiple etiologies. Cortical cerebellar atrophy (CCA), idiopathic late-onset cerebellar ataxia and sporadic adult-onset ataxia of unknown etiology have been used to refer to this disorder. These names describe key features of the disease, including degeneration limited to the cerebellar cortex (with or without secondary involvement of inferior olivary nucleus), slowly progressive ataxia and the absence of a clear etiology. <h3>Design/Methods:</h3> We studied two patients with rapidly progressive cerebellar ataxia and dementia. We performed postmortem evaluation of the brain and whole genome sequencing, as well as analysis of AAGGG pentanucleotide repeat expansion in the <i>RFC1</i>. <h3>Results:</h3> Case 1 was a 36-year-old man with a one-year history of ataxia and dementia. Case 2 was a 41-year-old woman with a 16-month history of ataxia and dementia. Extensive studies on autoimmune etiologies and prion disease were negative in both patients. Pathological findings were consistent with CCA, but there were also degenerative changes in the thalamus of both cases. Immunohistochemistry did not show prion protein deposits. Genetic analyses did not reveal any pathogenic variants associated with cerebellar ataxia or pathologic repeat expansion in the <i>RFC1</i> gene. <h3>Conclusions:</h3> Although the underlying etiology of rapidly progressive CCA is unknown, we propose that the combination of clinical and pathological features of CAA with a short disease course defines a new disease entity, which we refer to as rapidly progressive cerebellar cortical and thalamic degeneration (RPCCAT). <b>Disclosure:</b> Dr. Koga has nothing to disclose. Mr. Ali has nothing to disclose. Matthew Baker has nothing to disclose. Klaas Wierenga has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for BMC Medical Genomics . Dr. Dompenciel has nothing to disclose. Dr. Dickson has nothing to disclose. Dr. Wszolek has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Polish Neurological Society/Via Medica.

A novel clinicopathologic entity causing rapidly progressive cerebellar ataxia?

Sporadic, adult-onset cerebellar ataxia is a disease with multiple etiologies. In addition to cortical cerebellar atrophy (CCA), which is often used for the pathological diagnosis, other terms such as idiopathic late-onset cerebellar ataxia (ILOCA) and sporadic adult-onset ataxia of unknown etiology (SAOA) have been used to refer to this disorder. These names describe key features of the disease, including degeneration limited to the cerebellar cortex (with or without secondary involvement of inferior olivary nuclei), a slowly progressive ataxia, and absence of a clear etiology, such as multiple system atrophy, as well as paraneoplastic, autoimmune, infectious and inherited ataxias. In this Point of View article, we describe two patients with sporadic, adult-onset ataxia with rapidly progressive disease course in addition to extracerebellar symptoms resembling prion disease, including the reevaluation of one patient who was previously reported. Pathological findings are mostly consistent with CCA, but also have degenerative changes in the thalamus. Whole genome sequencing in two patients with rapidly progressive CCA did not reveal any pathogenic variants associated with cerebellar ataxia. Although the underlying etiology behind rapidly progressive CCA is unknown, we suggest that the unique combination of clinical and pathological features of CAA with a short disease course defines a new disease entity, rapidly progressive cerebellar cortical and thalamic degeneration. This viewpoint article draws attention to this rare sporadic cerebellar ataxia with the hope that highlighting clinical and pathologic findings in a typical case will lead to improved recognition and research.

Unravelling the etiology of sporadic late-onset cerebellar ataxia in a cohort of 205 patients: a prospective study.

Despite recent progress in the field of genetics, sporadic late-onset (> 40years) cerebellar ataxia (SLOCA) etiology remains frequently elusive, while the optimal diagnostic workup still needs to be determined. We aimed to comprehensively describe the causes of SLOCA and to discuss the relevance of the investigations. We included 205 consecutive patients with SLOCA seen in our referral center. Patients were prospectively investigated using exhaustive clinical assessment, biochemical, genetic, electrophysiological, and imaging explorations. We established a diagnosis in 135 (66%) patients and reported 26 different causes for SLOCA, the most frequent being multiple system atrophy cerebellar type (MSA-C) (41%). Fifty-one patients (25%) had various causes of SLOCA including immune-mediated diseases such as multiple sclerosis or anti-GAD antibody-mediated ataxia; and other causes, such as alcoholic cerebellar degeneration, superficial siderosis, or Creutzfeldt-Jakob disease. We also identified 11 genetic causes in 20 patients, including SPG7 (n = 4), RFC1-associated CANVAS (n = 3), SLC20A2 (n = 3), very-late-onset Friedreich's ataxia (n = 2), FXTAS (n = 2), SCA3 (n = 1), SCA17 (n = 1), DRPLA (n = 1), MYORG (n = 1), MELAS (n = 1), and a mitochondriopathy (n = 1) that were less severe than MSA-C (p < 0.001). Remaining patients (34%) had idiopathic late-onset cerebellar ataxia which was less severe than MSA-C (p < 0.01). Our prospective study provides an exhaustive picture of the etiology of SLOCA and clues regarding yield of investigations and diagnostic workup. Based on our observations, we established a diagnostic algorithm for SLOCA.

Reader Response: Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study.

We read with great interest the study by Wirth et al.1 The authors evaluate nigrostriatal dopaminergic denervation (NSDD) progression in 85 patients with sporadic late-onset cerebellar ataxia (SLOCA) using the [1231]-FP-CIT-SPECT, associated with SARA, UPDRS-III, and SDFS scores, to differentiate cerebellar multiple system atrophy (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). Their results indicate that 33 patients had probable MSA-C, 8 patients had possible MSA-C, and 44 patients had ILOCA.1

Author Response: Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study.

We thank Teive et al. for their valuable comments on our work.1 We agree that REM sleep behavior disorders (RBD) are a typical hallmark of α-synucleinopathies, including multiple system atrophy (MSA).2 Some pieces of evidence suggest that RBD could be useful in differentiating idiopathic late-onset cerebellar ataxia (ILOCA) from cerebellar MSA (MSA-C).3 It has also been shown that RBD could predate the onset of cerebellar syndrome in MSA-C; for this reason, it has recently been suggested to create a criteria set for possible prodromal MSA-C defined by the association of RBD with cerebellar ataxia.4

"Phalanx sign" helps to discriminate MSA-C from idiopathic late onset cerebellar ataxia.

Early diagnosis of MSA-C in patients with late-onset cerebellar ataxia (LOCA) may prove difficult. We therefore describe and evaluate the performance of the new "phalanx sign" (PS), that should be looked for during the nose-finger test to distinguish MSA-C from idiopathic late-onset ataxia (ILOCA). Sensitivity, specificity, positive predictive value, negative predictive value and interrater reliability of PS were assessed in three groups: 21 MSA-C, 23 ILOCA and 20 age-matched healthy subjects. PS was positive for 61.9% of MSA-C patients', 4.3% of ILOCA patients' and in none of healthy subjects' evaluations. PS discriminated MSA-C from ILOCA (p < 0.001) with a sensitivity of 61.9%, a specificity of 95.7%, a positive predictive value of 92.9%, a negative predictive value of 73.3% and a substantial interrater reliability (Kappa = 0.7273). PS could be a helpful, easy and reproducible sign for the early diagnosis of MSA-C in patients with LOCA.

Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study.

Nigrostriatal dopaminergic denervation (NSDD) remains poorly characterized in cerebellar multiple system atrophy (MSA-C). We aimed to study NSDD progression in MSA-C and evaluate the capacity for [123I]-FP-CIT-SPECT and parkinsonism to differentiate MSA-C from idiopathic late-onset cerebellar ataxia (ILOCA). We included 85 patients successively referred for sporadic late-onset cerebellar ataxia (SLOCA). Every 6 months, SARA, UPDRS-III, and SDFS scores were measured, and MSA-C diagnostic criteria were searched for. Striatal/occipital dopaminergic binding ratio was evaluated every year with [123I]-FP-CIT-scintigraphy. After a mean follow-up of 33.8 months, 33 patients had probable MSA-C, 8 possible MSA-C, and 44 ILOCA. SARA and UPDRS-III scores worsened faster in the probable MSA-C group (p < 0.01) compared with the ILOCA group. The baseline striatal/occipital ratio was lower (2.3 vs 2.97; p < 0.01) and more decreasing among patients with probable MSA-C (p < 0.01). Weighting dysautonomia and parkinsonism and/or NSDD as additional and principal criterion, respectively, in the possible MSA-C diagnostic criteria slightly improved their specificity (81.6% vs 76.9%) and sensitivity (77.8% vs 72.2%) to predict a final diagnosis of probable MSA-C. Rapid symptom worsening and NSDD existence and progression predict MSA-C among patients with SLOCA. Parkinsonism, NSDD, and dysautonomia should be considered equivalent for possible MSA-C diagnosis.

Social Cognition in Patients With Cerebellar Neurodegenerative Disorders.

ObjectiveCerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs.Materials and MethodsSocial cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood.ResultsCD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) – recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients’ achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT – Delayed free recall predicted their performance on the Faux Pas Recognition Test.ConclusionPatients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language.

Idiopathic very late-onset cerebellar ataxia: a Brazilian case series.

The authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy. 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG. 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients. We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

The Diagnosis and Natural History of Multiple System Atrophy, Cerebellar Type.

The objective of this study was to identify key features differentiating multiple system atrophy cerebellar type (MSA-C) from idiopathic late-onset cerebellar ataxia (ILOCA). We reviewed records of patients seen in the Massachusetts General Hospital Ataxia Unit between 1992 and 2013 with consensus criteria diagnoses of MSA-C or ILOCA. Twelve patients had definite MSA-C, 53 had possible/probable MSA-C, and 12 had ILOCA. Autonomic features, specifically urinary urgency, frequency, and incontinence with erectile dysfunction in males, differentiated MSA-C from ILOCA throughout the disease course (p = 0.005). Orthostatic hypotension developed later and differentiated MSA-C from ILOCA (p < 0.01). REM sleep behavior disorder (RBD) occurred early in possible/probable MSA-C (p < 0.01). Late MSA-C included pathologic laughing and crying (PLC, p < 0.01), bradykinesia (p = 0.01), and corticospinal findings (p = 0.01). MRI distinguished MSA-C from ILOCA by atrophy of the brainstem (p < 0.01) and middle cerebellar peduncles (MCP, p = 0.02). MSA-C progressed faster than ILOCA: by 6years, MSA-C walker dependency was 100% and ILOCA 33%. MSA-C survival was 8.4 ± 2.5years. Mean length of ILOCA illness to date is 15.9 ± 6.4years. A sporadic onset, insidiously developing cerebellar syndrome in midlife, with autonomic features of otherwise unexplained bladder dysfunction with or without erectile dysfunction in males, and atrophy of the cerebellum, brainstem, and MCP points strongly to MSA-C. RBD and postural hypotension confirm the diagnosis. Extrapyramidal findings, corticospinal tract signs, and PLC are helpful but not necessary for diagnosis. Clarity in early MSA-C diagnosis can prevent unnecessary investigations and facilitate therapeutic trials.

Idiopathic late-onset cerebellar ataxia with cerebellar atrophy in a patient diagnosed with Chiari I malformation: a case report

Idiopathic late-onset cerebellar ataxia with cerebellar atrophy in a patient diagnosed with Chiari I malformation: a case report

Progression of Idiopathic Late Onset Cerebellar Ataxia (S12.006)

Objective: To analyze the follow-up of idiopathic late onset cerebellar ataxia (ILOCA) patients. Background ILOCA patients represent a group of neurodegenerative diseases of unknown cause affecting the cerebellum and its afferent and efferent connections. Design/Methods: Clinical and laboratory observations of the course of 50 adult patients initially evaluated in an cerebellar ataxia outpatient clinic over 20 years, with a diagnosis of ILOCA, and followed up regularly. The presence of REM sleep behavior disorder (RBD) was evaluated as probable RBD, based on clinical validated criteria, or definite RBD, based on polysomnographic confirmation. Results: From a total of 50 patients with ILOCA (excluding all patients with acquired or genetically defined cerebellar ataxia), 24 subsequently developed criteria for MSA type-C. 26 patients remained with the diagnosis of ILOCA, among them 8 with a probable diagnosis of late cerebellar atrophy of Marie-Foix-Alajouanine syndrome (MFAS). The group of patients with late cerebellar atrophy of MFAS had an older mean age (72.8 years) than MSA-C patients (59.5 years). Neurological examination, including a thorough eye movement assessment did not differentiate patients with MSA-C and ILOCA. Clinically or definite RBD was diagnosed in 46 % of patients. However, patients who developed MSA type C had a highly percentage of probable and definite previously diagnosis of RBD (83.4%). On the other hand, among patients with ILOCA, the percentage of RBD was significantly lower (11.5%, p Conclusions: In this Brazilian series of ILOCA patients, MSA-C was clinically diagnosed in 48 % of cases and 52 % remained with the diagnosis of ILOCA, including a 12 % with the diagnosis of late cerebellar atrophy of MFAS. RBD diagnosis, either clinical or polysomnographic should included as an important tool in the differentiation of MSA type C and ILOCA. Disclosure: Dr. Teive has nothing to disclose. Dr. Munhoz has nothing to disclose. Dr. Arruda has nothing to disclose. Dr. Werneck has nothing to disclose.

1600 The utility of SOX antibodies for cancer prediction in patients with paraneoplastic neurological disorders

Recent studies have identified antibodies to the SOXB1 group of proteins in patients with paraneoplastic disorders (PNDs) associated with small-cell lung cancer (SCLC), particularly Lambert-Eaton myasthenic syndrome (LEMS), but rarely...

AMACR mutations cause late-onset autosomal recessive cerebellar ataxia

Progressive cerebellar disorders presenting in late middle age often have a structural, toxic, inflammatory, or endocrine basis. Having excluded these causes, many patients are given a clinical diagnosis of multiple systems atrophy type C, or idiopathic late-onset cerebellar ataxia, and not investigated further. Here we describe a sporadic cerebellar syndrome leading to the diagnosis of a rare metabolic disorder with important implications for treatment. ### Case report. A 58-year-old man presented with an 8-year history of gait unsteadiness, slurred speech, a few tonic/clonic seizures, and a decline in short-term memory. There was no relevant family history or consanguinity. On examination, he had a cerebellar dysarthria with appendicular and gait ataxia. Deep tendon reflexes were preserved, and plantar responses flexor. His Mini-Mental State Examination test score was 19/23 at 51 years of age, and 21/30 at age 58, with an Addenbrooke cognitive assessment of 61/100. Routine hematology, thyroid function, vitamin E, B12, and copper studies were normal. CSF examination revealed normal protein content, cell count, and no oligoclonal bands. Urinary amino and organic acids, hexosaminidase, and acylcarnitines were normal. Echocardiography was normal. An EEG showed a mild generalized …

Arginine test is not reliable for diagnosing cerebellar multiple system atrophy

We evaluated the arginine growth hormone (GH) stimulation test for the diagnosis of cerebellar-type multiple system atrophy (MSAc) in patients with ataxia. Fourteen subjects with MSAc, 11 with idiopathic late-onset cerebellar ataxia (ILOCA), 10 with familial ataxia, and 10 healthy controls were tested. After pituitary GH deficiency was excluded, subjects underwent arginine testing. Peak serum GH response was analyzed. No significant differences in peak GH response were found between subject populations. Thirty-three percent of MSAc subjects mounted responses >10 microg/l GH. Thirty-six percent of ILOCA subjects and 40 percent of healthy controls mounted responses <4 microg/l GH. Arginine thus appears to be unreliable for the diagnosis of MSAc.

Prolonged P3 latency and decreased brain perfusion in cerebellar degeneration.

To clarify the underlying mechanism of cognitive impairments in patients with cerebellar degeneration using event-related potentials (ERPs) and regional brain perfusion measurement. The P3 latency of ERPs was measured during a visual discrimination task in 15 patients with idiopathic late-onset cerebellar ataxia (ILOCA) and 10 age-matched control subjects. Regional brain perfusion was measured by single photon emission computed tomography using N-isopropyl-p[123I] iodoamphetamine. The mean P3 latency was longer in the patients than in controls. The patients showed lower perfusion in the frontal cortex and in the cerebellum than control subjects. There was a significant correlation between perfusion of the frontal cortex and cerebellum. The results indicate that patients with ILOCA exhibit slowing of cognitive information processing and suggest that its cognitive slowing may be due to a disruption of neural circuits between the cerebellum and the frontal cortex.

CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia

Differentiating idiopathic late-onset cerebellar ataxia (ILOCA) from ataxia due to the cerebellar subtype of multiple-system atrophy (MSA-C) can be difficult in the early stages of the disease The authors analyzed the levels of various CSF biomarkers in 27 patients with MSA-C and 18 patients with ILOCA and obtained cut-off points for each potential biomarker to differentiate MSA-C from ILOCA. Increased levels of neurofilament light chain (NFL) and neurofilament heavy chain (NFHp35) and decreased levels of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindoleaceticacid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) were observed in MSA-C compared with ILOCA patients. Receiver operating characteristic analysis showed high sensitivity and specificity levels for NFL, NFHp35, and MHPG analysis. At a cut-off of 24.4 ng/L for the NFL analysis, a sensitivity of 79% and a specificity of 94% were obtained for differentiating MSA-C from ILOCA. At a cut-off point for NFHp35 of 129.5 ng/L, sensitivity was 87% and specificity 83%. Analysis of MHPG levels (cut-off 42.5 nM) resulted in a sensitivity of 86% with a specificity of 75%. A multivariate logistic regression model selected NFL, MHPG, and tau as independent predictive biomarkers that separated the MSA-C and ILOCA groups. Increased levels of neurofilament light chain and tau and decreased levels of 3-methoxy-4-hydroxyphenylethyleneglycol were associated with high accuracy levels in differentiating the cerebellar subtype of multiple-system atrophy from idiopathic late-onset cerebellar ataxia (LOCA). CSF analysis may thus serve as a useful tool in early diagnostic differentiation of LOCA.

Olivopontocerebellar atrophy: Toward a better nosological definition

Olivopontocerebellar atrophy (OPCA) is a pathological label implying not only olivopontocerebellar changes, but also cases with more widespread lesions involving the CNS. This polytopic pathological background accounts for clinical complexity, essentially defined as cerebellar-plus syndrome. The term "OPCA" is applicable to an increasing number of neurodegenerative syndromes, including autosomal dominant ataxia, complicated spastic paraplegia, multiple-system atrophy (MSA), and many cases of idiopathic late-onset cerebellar ataxia (ILOCA), some of whom also turn out to have MSA. OPCA may also be part of the pathological hallmark of other disorders, such as prion disorders, mitochondrial encephalomyopathies, and hereditary metabolic diseases. Sporadic OPCA and ILOCA with cerebellar-plus presentation and neuroimaging evidence of brainstem and cerebellar atrophy may represent interchangeable eponyms. Just a quarter of such cases evolve to MSA within 5 years of the onset of symptoms. Therefore, the assumption that MSA and sporadic OPCA necessarily are one and the same disease is no longer tenable. Our review suggests that the label "OPCA" is useful to designate a clinicopathological syndrome that has a variety of etiologies carrying a poor prognosis, particularly if associated with autonomic failure as occurs in MSA.