Progressive Brain Atrophy Research Articles

Epidemiological Approaches to Understanding the Link Between Type 2 Diabetes and Dementia.

Diabetes and dementia are two diseases that increased dramatically in most societies in direct proportion to increases in average life expectancy. The two conditions are strongly associated and there is much hope that understanding this association will unlock the enigma that is the pathogenesis of dementia. Previous studies suggest that type 2 diabetes is a risk factor for all-cause dementia, vascular dementia and Alzheimer's disease. However these estimates may not necessarily have taken into account the overlap in dementia pathologies or the competing risk of death. Although the link between diabetes and vascular disease is intuitive, it is now becoming clear that type 2 diabetes is also associated with reduced brain volumes and with progression of brain atrophy, apparently independent of its relation with cerebrovascular disease. This raises the possibility that type 2 diabetes may also contribute to neurodegeneration, and particularly tau pathology. Prospective studies that record extensive multimodal in-vivo biomarkers and conduct rigorous postmortem neuropathological examination are certainly required to tease apart these complex pathways. However monitoring cognitive outcomes from current observational studies and randomized clinical trials of new diabetes treatments could be equally valuable in reducing the dementia epidemic.

A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients

Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (n = 4), moderate (n = 13) or severe (n = 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.

SIDEDNESS OF CAROTID ARTERY STENOSIS AND BRAIN VOLUME LOSS IN THE LEFT AND RIGHT HEMISPHERE: THE SMART-MR STUDY

Previous studies found an association between carotid stenosis degree and progression of brain atrophy, however no study reported on the relationship between sidedness of carotid stenosis and brain volume in the left and right hemispheres. We assessed the association between carotid stenosis side and changes in cerebral hemispheric volumes in patients with vascular disease. Within the SMART-MR study 1.5tesla MRI was performed in 1232 patients at baseline (mean age 58±10 years) and 663 after 4 years of follow-up. Carotid artery stenosis duplex measurements were performed at baseline and stenosis was defined at the cutpoint of 70%. Automated brain segmentation was used to quantify brain volumes and CSF. Volumes of the left and right hemispheres were calculated using the midsagittal surface. Using ANCOVA mean volume at baseline and mean change in volume between baseline and follow-up of the left and right hemisphere was estimated across 4 groups: no stenosis; left-sided stenosis only; right-sided stenosis only; bilateral stenosis adjusting for age and sex. In the total sample, brain volume (BV) of the left hemisphere was smaller than the right hemisphere (mean difference -1.06 %ICV; 95% CI -1.13 to -1.00) but this difference did not increase with age. Cross-sectionally, compared to participants without stenosis, those with left-sided stenosis had significantly smaller volume of the left but not the right hemisphere. However, right-sided stenosis was associated with smaller volumes of both hemispheres (Figure 1A). Similarly, in the longitudinal analysis a significant decrease in volume of both hemispheres was found in participants with right-sided stenosis, but not for left-sided stenosis (Figure 1B). In this population, as opposed to left-sided stenosis, right-sided stenosis results in brain volume reduction in both hemispheres. Studies should investigate whether other factors may explain this association or whether brain hemispheres have differential vulnerability to risk factors with aging. Left and right brain volumes in 4 groups: without carotid stenosis, left-sided stenosis, right-sided stenosis and bilateral stenosis. Bars represent mean (standard error) BV as % ICV. * p < 0.05 for difference in BV compared to corresponding hemisphere of the group without carotid stenosis (mean difference left hemisphere in left-sided stenosis -0.86 %lCV; 95% Cl -1.55 to -0.17, right hemisphere in right-sided stenosis -1.28 %ICV; 95% CI -1.90 to -0.67). Δp = 0.06 for difference in BV compared to the left hemisphere of the group without carotid stenosis (mean difference -0.60 %lCV; 95% Cl -1.22 to 0.03). lCV = intracranial volume. Longitudinal association between carotid stenosis groups and change in BV. Bars represent mean (standard error) change in BV as % ICV after a mean 3.9 years of follow-up. * p < 0.05 for decrease in BV compared to corresponding hemisphere of the group without carotid stenosis (mean difference left hemisphere in right-sided stenosis -0.45 %ICV; 95% CI -0.86 to -0.03, right hemisphere in right-sided stenosis -0.95 %ICV; 95%CI -1.37 to -0.53, left hemisphere in bilateral stenosis -0.81 %ICV; 95% CI -1.36 to -0.29, right hemisphere in bilateral stenosis -0.62 %ICV; 95% CI -1.16 to -0.09). ICV = intracranial volume.

Serial brain MRI findings in a rare survivor of rabies encephalitis.

Rabies is a neurotropic viral illness, almost always fatal, that is equally dreaded by healthcare practitioners and patients due to the dismal prognosis and limited treatment options once symptoms set in. There are hardly any reports on MRI changes in the brain in survivors of rabies encephalitis. We present the clinical course and the imaging findings on serial MRI examinations in a rare patient who survived rabies infection. Initial brain MRI done 8 days after onset of symptoms revealed bilaterally symmetrical non-enhancing areas of T1 and T2 hyperintensity in the basal ganglia, thalami, mid brain, and pons along with T2 hyperintensity and restricted diffusion in fronto-parietal cortical grey matter and left hippocampus. Subsequent MRI scans at 2 months and 5 months revealed progressive brain atrophy, leukoencephalopathy, and gliosis.

Protease-activated receptor-1 activation by granzyme B causes neurotoxicity that is augmented by interleukin-1\u03b2

BackgroundThe cause of neurodegeneration in progressive forms of multiple sclerosis is unknown. We investigated the impact of specific neuroinflammatory markers on human neurons to identify potential therapeutic targets for neuroprotection against chronic inflammation.MethodsSurface immunocytochemistry directly visualized protease-activated receptor-1 (PAR1) and interleukin-1 (IL-1) receptors on neurons in human postmortem cortex in patients with and without neuroinflammatory lesions. Viability of cultured neurons was determined after exposure to cerebrospinal fluid from patients with progressive multiple sclerosis or purified granzyme B and IL-1β. Inhibitors of PAR1 activation and of PAR1-associated second messenger signaling were used to elucidate a mechanism of neurotoxicity.ResultsImmunohistochemistry of human post-mortem brain tissue demonstrated cells expressing higher amounts of PAR1 near and within subcortical lesions in patients with multiple sclerosis compared to control tissue. Human cerebrospinal fluid samples containing granzyme B and IL-1β were toxic to human neuronal cultures. Granzyme B was neurotoxic through activation of PAR1 and subsequently the phospholipase Cβ-IP3 second messenger system. Inhibition of PAR1 or IP3 prevented granzyme B toxicity. IL-1β enhanced granzyme B-mediated neurotoxicity by increasing PAR1 expression.ConclusionsNeurons within the inflamed central nervous system are imperiled because they express more PAR1 and are exposed to a neurotoxic combination of both granzyme B and IL-1β. The effects of these inflammatory mediators may be a contributing factor in the progressive brain atrophy associated with neuroinflammatory diseases. Knowledge of how exposure to IL-1β and granzyme B act synergistically to cause neuronal death yields potential novel neuroprotective treatments for neuroinflammatory diseases.

Progression of Whole Brain and Gray Matter Atrophy in Relapsing MS Despite Treatment with Natalizumab (P5.357)

Progression of Whole Brain and Gray Matter Atrophy in Relapsing MS Despite Treatment with Natalizumab (P5.357)

Lymphomatosis cerebri showing transient spontaneous regression

AbstractWe describe the case of a 35‐year‐old man who presented with a seizure. Brain magnetic resonance imaging showed multiple white matter lesions in the cerebral hemispheres. His seizure was controllable with antiepileptics, and he remained asymptomatic for the next 4 months with follow‐up magnetic resonance imaging showing transient spontaneous regression. However, he developed progressive decline in cognitive functions approximately 1 year after symptom onset. Magnetic resonance imaging showed recurrence of the white matter lesions and progression of brain atrophy. A brain biopsy established the pathological diagnosis of diffuse large B‐cell lymphoma, and he was clinically diagnosed with lymphomatosis cerebri. Lymphomatosis cerebri is a rare variant of primary central nervous system lymphoma characterized by diffuse infiltration of lymphomatous cells into the brain without forming a cohesive tumor mass. Although the clinical and radiographic course is rapidly progressive in the great majority of patients with lymphomatosis cerebri, transient spontaneous regression can occur, posing diagnostic challenges for physicians.

Hodges’ Frontotemporal Dementia, Second Edition

Hodges’ Frontotemporal Dementia, Second Edition

Loss of spatacsin function alters lysosomal lipid clearance leading to upper and lower motor neuron degeneration

Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations. Mutations in the same gene are also responsible for rare forms of Charcot-Marie-Tooth (CMT) disease and progressive juvenile-onset amyotrophic lateral sclerosis (ALS). To elucidate the physiopathological mechanisms underlying these human pathologies, we disrupted the Spg11 gene in mice by inserting stop codons in exon 32, mimicking the most frequent mutations found in patients. The Spg11 knockout mouse developed early-onset motor impairment and cognitive deficits. These behavioral deficits were associated with progressive brain atrophy with the loss of neurons in the primary motor cortex, cerebellum and hippocampus, as well as with accumulation of dystrophic axons in the corticospinal tract. Spinal motor neurons also degenerated and this was accompanied by fragmentation of neuromuscular junctions and muscle atrophy. This new Spg11 knockout mouse therefore recapitulates the full range of symptoms associated with SPG11 mutations observed in HSP, ALS and CMT patients. Examination of the cellular alterations observed in this model suggests that the loss of spatacsin leads to the accumulation of lipids in lysosomes by perturbing their clearance from these organelles. Altogether, our results link lysosomal dysfunction and lipid metabolism to neurodegeneration and pinpoint a critical role of spatacsin in lipid turnover.

Serum neurofilament is associated with progression of brain atrophy and disability in early MS.

To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay. Longitudinal serum samples were available from 22 riluzole and 20 placebo participants over 24 months. There was no observed treatment effect with riluzole. Nf light chain (NfL) levels decreased over time (p = 0.007 at 24 months), whereas the Nf heavy chain was unchanged (p = 0.997). Changes in NfL were correlated with EDSS change (p = 0.009) and neuropsychological outcomes. Brain volume decreased more rapidly in patients with high baseline NfL (p = 0.05 at 12 months and p = 0.008 at 24 months) and this relationship became stronger at 24 months (p = 0.024 for interaction). Higher and increasing NfL predicted higher number of gadolinium-enhancing lesions (p < 0.001 for both). Our findings support the potential value of serum NfL as a marker of neuroaxonal injury in early multiple sclerosis. Its reduction over time could represent regression to the mean, or a possible treatment effect of IFN-β-1a. The association with whole brain atrophy and the formation of acute white matter lesions has relevant implications to use serum NfL as a noninvasive biomarker of the overall consequences of brain damage and ongoing disease activity. NCT00501943.

Progressive Brain Atrophy in Alternating Hemiplegia of Childhood.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder that includes involuntary movements, paroxysmal symptoms, and various severities of nonparoxysmal symptoms. To investigate the occurrence of structural brain abnormalities in patients with AHC during clinical courses. Conventional brain magnetic resonance imaging findings and clinical courses were retrospectively investigated in 14 patients with AHC confirmed by ATP1A3 mutations. Progressive frontal dominant cerebral, diffuse cerebellar cortical, and severe hippocampal atrophy were observed in seven patients with irreversible severe motor and intellectual deterioration. All of these seven patients exhibited status epilepticus and required transient respiratory care. Isolated diffuse cerebellar cortical atrophy was observed in two adult patients with mild motor regression. Five patients without apparent deterioration displayed almost normal brain findings. The areas of atrophy were consistent with the areas of increased expression of the Na+/K+-ATPase α3 subunit encoded by ATP1A3. Some of paroxysmal and nonparoxysmal neurological symptoms are considered as related to the areas of brain atrophy.

Neuroprotective effects of vascular endothelial growth factor A in the experimental autoimmune encephalomyelitis model of multiple sclerosis

Neuroprotective effects of vascular endothelial growth factor A in the experimental autoimmune encephalomyelitis model of multiple sclerosis

MR findings of Creutzfeldt-Jakob disease: a rare entity

Creutzfeldt-Jakob disease (CJD) is a prion disease that causes progressive dementia and is invariably fatal. This results from the misfolding of normal cellular prion proteins into an abnormal conformation. Prompt diagnosis is essential to prevent human-to-human transmission. On MR imaging, CJD shows high T2 signal in basal ganglia and cerebral cortex, as well as progressive brain atrophy. However, diffusion weighted imaging (DWI) is more sensitive in the diagnosis by showing restricted diffusion as high signal on DWI image and low signal on ADC map. In this case report, we will discuss the clinical presentation and imaging features of CJD. We will also discuss the disease entities which can mimic CJD.

Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis.

Background A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS. Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results There was a significant (p<0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum. Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively. The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001). The serum lactate dehydrogenase activity was also highly significantly raised (p<10-12) in patients with secondary progressive multiple sclerosis. Conclusions An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe2+) is chelated by haemoglobin.

Early diagnosis and outcome prediction of neonatal hypoxic-ischemic encephalopathy with color Doppler ultrasound.

To describe the ultrasound presentation of the brain and cerebral hemodynamics in neonates with hypoxic-ischemic encephalopathy (HIE) by comparison with control subjects. During June2012 to April2013, full term neonates who had clinical evidence of HIE were enrolled. Healthy newborns without HIE were used as a control group. Cerebral parenchyma, size of lateral ventricles and hemodynamic parameters of cerebral arteries were studied using two-dimensional duplex and color Doppler ultrasound. Neonates with moderate and severe HIE were followed-up with ultrasound for at least 3months. A total of 158consecutive neonates (82boys and 76girls), including 54 with mild HIE, 60 with moderate HIE and 44 with severe HIE were included. One hundred and twenty healthy newborns were randomly selected as a control group. Abnormal ultrasound findings of brain parenchyma were found in 25/54 (46.3%) neonates with mild HIE whereas they were found in 58/60 (96.7%) neonates with moderate HIE and 44/44 (100%) neonates with severe HIE. Almost all neonates with severe HIE had decreased cerebral artery blood flow velocity and increased resistance index of cerebral arteries. Of the 104neonates with moderate or severe HIE, follow-up ultrasound examination revealed cystic parenchymal lesions in 12/104 (11.5%), progressive ventricular dilatation and brain atrophy in 12/104 (11.5%), mild ventricular dilatation in 15/104 (14.4%) and leukoencephalomalacia in 2/104 (1.9%) neonates. Ultrasound features such as the size of lateral ventricles, altered brain parenchymal echogenicity and cerebral blood flow parameters are useful for the early diagnosis of HIE and help predict outcome.

Suppressing N-Acetyl-l-Aspartate Synthesis Prevents Loss of Neurons in a Murine Model of Canavan Leukodystrophy.

This is the first demonstration of cortical and cerebellar neuron depletion and progressive cerebral cortical thinning in an animal model of Canavan disease. Genetic suppression of N-acetyl-l-aspartate (NAA) synthesis, previously shown to block brain vacuolation in aspartoacylase-deficient mice, also prevents neuron loss and cerebral cortical atrophy in these mice. These results suggest that lowering the concentration of NAA in the brains of children with Canavan disease would prevent or slow progression of neurological deficits.

Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis

Background: A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods: We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS. Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results: There was a significant (p<0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum. Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively. The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001). The serum lactate dehydrogenase activity was also highly significantly raised (p<10 -12) in patients with secondary progressive multiple sclerosis. Conclusions: The results are consistent with the following hypothesis. In progressive multiple sclerosis, low-grade chronic intravascular haemolysis releases haemoglobin into the serum; the haemoglobin is subsequently translocated into the central nervous system (CNS) across the damaged blood-brain barrier. In the CNS, the haemoglobin and its breakdown products, including haem and iron, contribute to the neurodegeneration and consequent brain atrophy seen in progressive disease. We postulate that haemoglobin is a source of the iron whose deposition along blood vessels in multiple sclerosis plaques is associated with neurodegeneration. If so, then chelators of haemoglobin, rather than chelators of free serum iron, may be effective in preventing this neurodegeneration.

Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis

Background: A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods: We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS. Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results: There was a significant (p&lt;0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum. Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively. The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p&lt;0.001). The serum lactate dehydrogenase activity was also highly significantly raised (p&lt;10-12) in patients with secondary progressive multiple sclerosis. Conclusions: An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe2+) is chelated by haemoglobin.

Neuroanatomical correlates of prion disease progression - a 3T longitudinal voxel-based morphometry study.

PurposeMRI has become an essential tool for prion disease diagnosis. However there exist only a few serial MRI studies of prion patients, and these mostly used whole brain summary measures or region of interest based approaches. We present here the first longitudinal voxel-based morphometry (VBM) study in prion disease. The aim of this study was to systematically characterise progressive atrophy in patients with prion disease and identify whether atrophy in specific brain structures correlates with clinical assessment.MethodsTwenty-four prion disease patients with early stage disease (3 sporadic, 2 iatrogenic, 1 variant and 18 inherited CJD) and 25 controls were examined at 3T with a T1-weighted 3D MPRAGE sequence at multiple time-points (2–6 examinations per subject, interval range 0.1–3.2 years). Longitudinal VBM provided intra-subject and inter-subject image alignment, allowing voxel-wise comparison of progressive structural change. Clinical disease progression was assessed using the MRC Prion Disease Rating Scale. Firstly, in patients, we determined the brain regions where grey and white matter volume change between baseline and final examination correlated with the corresponding change in MRC Scale score. Secondly, in the 21/24 patients with interscan interval longer than 3 months, we identified regions where annualised rates of regional volume change in patients were different from rates in age-matched controls. Given the heterogeneity of the cohort, the regions identified reflect the common features of the different prion sub-types studied.ResultsIn the patients there were multiple regions where volume loss significantly correlated with decreased MRC scale, partially overlapping with anatomical regions where yearly rates of volume loss were significantly greater than controls. The key anatomical areas involved included: the basal ganglia and thalamus, pons and medulla, the hippocampal formation and the superior parietal lobules. There were no areas demonstrating volume loss significantly higher in controls than patients or negative correlation between volume and MRC Scale score.ConclusionsUsing 3T MRI and longitudinal VBM we have identified key anatomical regions of progressive volume loss which correlate with an established clinical disease severity index and are relevant to clinical deterioration. Localisation of the regions of progressive brain atrophy correlating most strongly with clinical decline may help to provide more targeted imaging endpoints for future clinical trials.

Progression of brain atrophy in PSP and CBS over 6 months and 1 year.

To examine the utility and reliability of volumetric MRI in measuring disease progression in the 4 repeat tauopathies, progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), to support clinical development of new tau-directed therapeutic agents. Six- and 12-month changes in regional MRI volumes and PSP Rating Scale scores were examined in 55 patients with PSP and 33 patients with CBS (78% amyloid PET negative) compared to 30 normal controls from a multicenter natural history study. Longitudinal voxel-based morphometric analyses identified patterns of volume loss, and region-of-interest analyses examined rates of volume loss in brainstem (midbrain, pons, superior cerebellar peduncle), cortical, and subcortical regions based on previously validated atlases. Results were compared to those in a replication cohort of 226 patients with PSP with MRI data from the AL-108-231 clinical trial. Patients with CBS exhibited greater baseline atrophy and greater longitudinal atrophy rates in cortical and basal ganglia regions than patients with PSP; however, midbrain and pontine atrophy rates were similar. Voxel-wise analyses showed distinct patterns of regional longitudinal atrophy in each group as compared to normal controls. The midbrain/pons volumetric ratio differed between diagnoses but remained stable over time. In both patient groups, brainstem atrophy rates were correlated with disease progression measured using the PSP Rating Scale. Volume loss is quantifiable over a period of 6 months in CBS and PSP. Future clinical trials may be able to combine CBS and PSP to measure therapeutic effects.