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BACKGROUND: The difficulties and challenges faced by people with Parkinson's disease (PD) in performing daily orofacial function are not systematically investigated. In this study, specific orofacial non-motor and motor symptoms and functions were systematically examined in PD patients in comparison to a matched control group.METHODS: The clinical case-controlled study was conducted from May 2021 to October 2022 and included persons with PD and age- and gender-matched persons without PD. The participants with PD were outpatients diagnosed with PD at the Department of Neurology at Bispebjerg University Hospital in Copenhagen, Denmark. The participants underwent a systematic clinical and relevant self-assessment of the orofacial function and temporomandibular disorders (TMD). The primary outcomes were objective and subjective assessments of the general orofacial function, mastication, swallowing, xerostomia and drooling. The secondary outcomes were the prevalence of TMD and orofacial pain. The difference in outcome measures between the two groups was analysed using chi-square and Mann-Whitney U test.RESULTS: The study included 20 persons with PD and 20 age- and gender-matched persons without PD. Both objectively and subjectively, persons with PD had poorer orofacial function than the control group. Persons with PD had also a significantly more severe limitation of jaw mobility and jaw function. The objective masticatory function was also significantly reduced for persons with PD compared to the control group, and 60% of persons with PD found it difficult to eat foods with certain consistencies while 0% of the control group reported that problem. Persons with PD could swallow less water per second and the average swallowing event was significantly longer for PD persons. Even though PD persons reported more xerostomia (58% for persons with PD and 20% for control persons), they also reported significantly more drooling than the control group. Additionall

BACKGROUND: The difficulties and challenges faced by people with Parkinson's disease (PD) in performing daily orofacial function are not systematically investigated. In this study, specific orofacial non-motor and motor symptoms and functions were systematically examined in PD patients in comparison to a matched control group.METHODS: The clinical case-controlled study was conducted from May 2021 to October 2022 and included persons with PD and age- and gender-matched persons without PD. The participants with PD were outpatients diagnosed with PD at the Department of Neurology at Bispebjerg University Hospital in Copenhagen, Denmark. The participants underwent a systematic clinical and relevant self-assessment of the orofacial function and temporomandibular disorders (TMD). The primary outcomes were objective and subjective assessments of the general orofacial function, mastication, swallowing, xerostomia and drooling. The secondary outcomes were the prevalence of TMD and orofacial pain. The difference in outcome measures between the two groups was analysed using chi-square and Mann-Whitney U test.RESULTS: The study included 20 persons with PD and 20 age- and gender-matched persons without PD. Both objectively and subjectively, persons with PD had poorer orofacial function than the control group. Persons with PD had also a significantly more severe limitation of jaw mobility and jaw function. The objective masticatory function was also significantly reduced for persons with PD compared to the control group, and 60% of persons with PD found it difficult to eat foods with certain consistencies while 0% of the control group reported that problem. Persons with PD could swallow less water per second and the average swallowing event was significantly longer for PD persons. Even though PD persons reported more xerostomia (58% for persons with PD and 20% for control persons), they also reported significantly more drooling than the control group. Additionall

Aim: This is a long-term open follow-up of a prospective double-blind crossover study, where electrodes were bilaterally implanted in both the Subthalamic nucleus (STN) and internal pallidum (GPi) in patients with isolated dystonia.Methods: Patients with isolated dystonia were included to undergo surgery with Deep Brain stimulation (DBS) and after randomization, in a double-blind cross-over study, receiving bilateral stimulation of either STN or GPi for 6 months in each target. Preoperative and postoperative assessments with the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and the 36-item Short Form Health Survey (SF-36) were performed. In this long-term follow-up (LFU), these ratings were repeated, and patients were evaluated with cognitive tests.Results: 21 patients were included in the protocol, 9 patients with generalized dystonia, 12 with a diagnosis of cervical dystonia. The mean duration of disease was 19.3 years, age at time of surgery 50.1 years. Fourteen patients participated in the LFU. At a mean follow-up of 10.2 years (range 4.8-15.4), BFMDRS movement score was improved with a mean of 36% (p < 0.05) compared with baseline. At LFU both a statistically significant improvement of stimulation in STN on BFMDRS movement score (p = 0.029) and Gpi (p = 0.008) was demonstrated, no significant difference was found between the two targets (p = 0.076). SF-36 improved for both targets.Conclusion: In this study we performed a long-term follow-up in 14 patients with cervical or generalized dystonia, who received stimulation in GPi, STN or both. The mean follow-up time was more than 10 years. Our data support a long-term effect of both STN-DBS and GPi-DBS in dystonia with equal effect and safety for up to 15 years. STN has been proven a viable safe and effective target and may be used as an alternative to GPi in both adult-onset cervical dystonia and generalized dystonia.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. Objective: This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. Methods: The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. Results and conclusions: Both ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.

Anne-Lene Kjældgaard,1,2 Katrine Pilely,1 Karsten Skovgaard Olsen,2 Anne Øberg Lauritsen,2 Stephen Wørlich Pedersen,3 Kirsten Svenstrup,3,4 Merete Karlsborg,4 Helle Thagesen,5 Morten Blaabjerg,5 Ásta Theódórsdóttir,6 Elisabeth Gundtoft Elmo,3 Anette Torvin Møller,7 Niels Anker Pedersen,8 Niels Kirkegaard,8 Kirsten Møller,2,9 Peter Garred1,9 1Laboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Diagnostic Centre, Rigshospitalet, Copenhagen, Denmark; 2Department of Neuroanaesthesiology Neuroscience Centre, Rigshospitalet, Copenhagen, Denmark; 3Department of Neurology, Neuroscience Centre, Rigshospitalet, Copenhagen, Denmark; 4Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark; 5Department of Neurology, Roskilde University Hospital, Roskilde, Denmark; 6Department of Neurology, Odense University Hospital, Odense, Denmark; 7Department of Neurology, Aarhus Hospital, Copenhagen, Denmark; 8Department of Anaesthesiology, Private Hospital Gildhøj, Brondby, Denmark; 9Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Anne-Lene KjældgaardLaboratory of Molecular Medicine, Department of Clinical Immunology, Section 7631, Diagnostic Centre, Rigshospitalet, Ole Maaloesvej 26, Copenhagen, DK-2200, DenmarkTel +45 35457631Fax +45 35398766Email anne-lene.kjaeldgaard@regionh.dkBackground: The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients.Methods: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy c

BACKGROUND: Parkinson's disease (PD) has a negative effect on oral health and orofacial function, but the subjective experience of orofacial symptoms and their impact on the quality of life is not fully investigated. In addition, knowledge of how to improve the subjective oral symptoms is lacking.OBJECTIVES: To assess the self-reported orofacial function and oral health in patients with PD. Furthermore, to investigate the effect of interventions for improvement of oral hygiene and function on oral health related quality of life (OHRQoL).METHODS: A randomised controlled study with delayed intervention was conducted in 29 patients with moderate to advanced PD. Patients were instructed in a standardised exercise program for the jaw and orofacial muscles and given an individualized oral hygiene program. The effect on self-reported orofacial function and OHRQoL was measured after 2 and 4 months using the Nordic Orofacial Test - Screening (NOT-S), the oral health impact profile (OHIP-14), self-reported drooling score and subjective mastication ability.RESULTS: Self-reported oral health and function before the intervention was significantly correlated to the severity and duration of PD. The NOT-S and drooling score were significantly improved by the interventions after 2 months and the OHIP-14 after 4 months.CONCLUSION: The interventions improve the self-reported orofacial function and OHRQoL. These simple interventions can be implemented in the allied multidisciplinary healthcare surrounding the PD patient.

Background: The complement system has been suggested to be involved in the pathophy- siology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. Methods: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. Results: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of comple- ment markers and survival as estimated by hazard ratios. Conclusion: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiol- ogy of ALS.

BACKGROUND: Parkinson's disease (PD) has a negative effect on oral health and orofacial function, but the subjective experience of orofacial symptoms and their impact on the quality of life is not fully investigated. In addition, knowledge of how to improve the subjective oral symptoms is lacking.OBJECTIVES: To assess the self-reported orofacial function and oral health in patients with PD. Furthermore, to investigate the effect of interventions for improvement of oral hygiene and function on oral health related quality of life (OHRQoL).METHODS: A randomised controlled study with delayed intervention was conducted in 29 patients with moderate to advanced PD. Patients were instructed in a standardised exercise program for the jaw and orofacial muscles and given an individualized oral hygiene program. The effect on self-reported orofacial function and OHRQoL was measured after 2 and 4 months using the Nordic Orofacial Test - Screening (NOT-S), the oral health impact profile (OHIP-14), self-reported drooling score and subjective mastication ability.RESULTS: Self-reported oral health and function before the intervention was significantly correlated to the severity and duration of PD. The NOT-S and drooling score were significantly improved by the interventions after 2 months and the OHIP-14 after 4 months.CONCLUSION: The interventions improve the self-reported orofacial function and OHRQoL. These simple interventions can be implemented in the allied multidisciplinary healthcare surrounding the PD patient.

Background: The complement system has been suggested to be involved in the pathophy- siology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. Methods: This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, -2, and -3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. Results: Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of comple- ment markers and survival as estimated by hazard ratios. Conclusion: ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiol- ogy of ALS.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established and the most effective treatment for advanced Parkinson's disease (PD). However, little is known of the long-term effects. Objectives: The aim of this study was to examine the long-term effects of STN-DBS in PD and evaluate the effect of reprogramming after more than 8 years of treatment. Methods: A total of 82 patients underwent surgery in Copenhagen between 2001 and 2008. Before surgery and at 8 to 15 years follow-up, the patients were rated with the Unified Parkinson's Disease Rating Scale (UPDRS) with and without stimulation and medicine. Furthermore, at long-term follow-up, the patients were offered a systemic reprogramming of the stimulation settings. Data from patients' medical records were collected. The mean (range) age at surgery was 60 (42–78) years, and the duration of disease was 13 (5–25) years. A total of 30 patients completed the long-term follow-up. Results: The mean reduction of the motor UPDRS by medication before surgery was 52%. The improvement of motor UPDRS with stimulation alone compared with motor UPDRS with neither stimulation nor medication was 61% at 1 year and 39% at 8 to 15 years after surgery (before reprogramming). Compared with before surgery, medication was reduced by 55% after 1 year and 44% after 8 to 15 years. After reprogramming, most patients improved. Conclusions: STN-DBS remains effective in the long run, with a sustained reduction of medication in the 30 of 82 patients available for long-term follow-up. Reprogramming is effective even in the late stages of PD and after many years of treatment.

Neurodegenerativ sygdom er en paraplybetegnelse for en række lidelser, der påvirker neuroner i centralnervesystemet. Alzheimers sygdom og Parkinsons sygdom er de mest almindelige. Den gradvise og oftest langsomme nedbrydning af hjernen og dens funktioner medfører forskellige symptomer. Ved Alzheimers sygdom er hukommelsesbesvær og personlighed- og adfærdsændringer mest fremtrædende og ved Parkinsons sygdom bevægelsesbesvær. Det er vigtigt, at man som tandlæge er opmærksom på, at der er tale om langvarige og stadigt progredierende lidelser, og at de kognitive tab og hæmningen af den orofaciale funktion kun bliver alvorligere med tiden. Som konsekvens sker der en betydelig forringelse af den orale sundhed. Behandlingen kræver særlig indsigt og skal tilpasses det individuelle sygdomsforløb, hvor der efterhånden kræves mere hjælp til daglig mundhygiejne og mere radikale behandlingstiltag. Samarbejde med patientens læge og pårørende er væsentligt for indsigt i patienternes situation og aktuelle sygdomsstatus og medicin for at planlægge og give bedst mulig tandlægelig behandling.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established and the most effective treatment for advanced Parkinson's disease (PD). However, little is known of the long-term effects. Objectives: The aim of this study was to examine the long-term effects of STN-DBS in PD and evaluate the effect of reprogramming after more than 8 years of treatment. Methods: A total of 82 patients underwent surgery in Copenhagen between 2001 and 2008. Before surgery and at 8 to 15 years follow-up, the patients were rated with the Unified Parkinson's Disease Rating Scale (UPDRS) with and without stimulation and medicine. Furthermore, at long-term follow-up, the patients were offered a systemic reprogramming of the stimulation settings. Data from patients' medical records were collected. The mean (range) age at surgery was 60 (42–78) years, and the duration of disease was 13 (5–25) years. A total of 30 patients completed the long-term follow-up. Results: The mean reduction of the motor UPDRS by medication before surgery was 52%. The improvement of motor UPDRS with stimulation alone compared with motor UPDRS with neither stimulation nor medication was 61% at 1 year and 39% at 8 to 15 years after surgery (before reprogramming). Compared with before surgery, medication was reduced by 55% after 1 year and 44% after 8 to 15 years. After reprogramming, most patients improved. Conclusions: STN-DBS remains effective in the long run, with a sustained reduction of medication in the 30 of 82 patients available for long-term follow-up. Reprogramming is effective even in the late stages of PD and after many years of treatment.

n/a, Funding Agencies|Biogen Idec; Orphazyme ApS; Roche; Biogen; Merck Idec; Kedrion; Cytokinetics; Genzyme; Mitsubishi; Behring; Merz Parma Schweiz; Baxalta; Merck

n/a, Funding Agencies|Biogen Idec; Orphazyme ApS; Roche; Biogen; Merck Idec; Kedrion; Cytokinetics; Genzyme; Mitsubishi; Behring; Merz Parma Schweiz; Baxalta; Merck

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.

Parkinsonism and attention deficit hyperactivity disorder (ADHD) are widespread brain disorders that involve disturbances of dopaminergic signaling. The sodium-coupled dopamine transporter (DAT) controls dopamine homeostasis, but its contribution to disease remains poorly understood. Here, we analyzed a cohort of patients with atypical movement disorder and identified 2 DAT coding variants, DAT-Ile312Phe and a presumed de novo mutant DAT-Asp421Asn, in an adult male with early-onset parkinsonism and ADHD. According to DAT single-photon emission computed tomography (DAT-SPECT) scans and a fluoro-deoxy-glucose-PET/MRI (FDG-PET/MRI) scan, the patient suffered from progressive dopaminergic neurodegeneration. In heterologous cells, both DAT variants exhibited markedly reduced dopamine uptake capacity but preserved membrane targeting, consistent with impaired catalytic activity. Computational simulations and uptake experiments suggested that the disrupted function of the DAT-Asp421Asn mutant is the result of compromised sodium binding, in agreement with Asp421 coordinating sodium at the second sodium site. For DAT-Asp421Asn, substrate efflux experiments revealed a constitutive, anomalous efflux of dopamine, and electrophysiological analyses identified a large cation leak that might further perturb dopaminergic neurotransmission. Our results link specific DAT missense mutations to neurodegenerative early-onset parkinsonism. Moreover, the neuropsychiatric comorbidity provides additional support for the idea that DAT missense mutations are an ADHD risk factor and suggests that complex DAT genotype and phenotype correlations contribute to different dopaminergic pathologies.

To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning.

To examine the diagnostic sensitivity and specificity of dopamine transporter SPECT imaging with a highly dopamine transporter selective radioligand. The study included consecutively enrolled, drug-naive patients with an average short history of parkinsonian motor symptoms, referred for diagnostic scanning.

Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump. Monotherapy with continuous intestinal levodopa infusion to the duodenum (Duodopa) was introduced in 2004.

Patients with advanced Parkinson's disease (PD) often develop motor complications including fluctuations and involuntary movements (dyskinesias). In Denmark, treatment has comprised Deep Brain Stimulation (DBS) since the late 1990s, and as from 2002 use of a subcutaneous apomorphine pump. Monotherapy with continuous intestinal levodopa infusion to the duodenum (Duodopa) was introduced in 2004.

Background Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that can be difficult to diagnose and distinguish from each other. Study aims and methods Patients with PD and MSA and controls were studied with magnetic resonance imaging (MRI) using tissue segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. Results Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA patients had significantly smaller substantia nigra and caudate volumes than controls but normal intracranial volume. In both patient groups there was a further trend towards smaller amygdala volumes. Discussion Increased ICV in PD patients is a new finding that may be explained by genetic factors or compensatory responses to early CNS damage. Atrophy of the amygdala in MSA patients has not been demonstrated with MR before. It might explain why these patients can have hyposmia. The putaminal atrophy found in the PD group may be a trait of the later stages of PD. Segmentation of the substantia nigra can be a useful aid in the diagnosis of PD and MSA.

Background Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that can be difficult to diagnose and distinguish from each other. Study aims and methods Patients with PD and MSA and controls were studied with magnetic resonance imaging (MRI) using tissue segmentation and outlining of regions in order to identify regional volume changes that might be useful in the diagnosis of the two diseases. Results Patients with PD had significantly larger intracranial volumes (ICVs) and significantly smaller putaminal and sustantia nigra volumes than controls. MSA patients had significantly smaller substantia nigra and caudate volumes than controls but normal intracranial volume. In both patient groups there was a further trend towards smaller amygdala volumes. Discussion Increased ICV in PD patients is a new finding that may be explained by genetic factors or compensatory responses to early CNS damage. Atrophy of the amygdala in MSA patients has not been demonstrated with MR before. It might explain why these patients can have hyposmia. The putaminal atrophy found in the PD group may be a trait of the later stages of PD. Segmentation of the substantia nigra can be a useful aid in the diagnosis of PD and MSA.

BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to investigate the neuronal and axonal fibre distribution in the human brain. Changes in diffusion characteristics of water molecules in the white matter can be estimated as the apparent diffusion coefficient (ADC) and the fractional anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different levels in the corticospinal tract (CST) (corona radiata, internal capsule and pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or retrograde axonal degeneration. METHODS: We studied eight ALS patients with clinical signs of upper motor neuron involvement. The patients were compared with 11 healthy age-matched controls. RESULTS: ADC was significantly increased in the CST in ALS patients at the level of the internal capsule and also increased in the pons, but without statistical significance. ADC was unchanged at the level of the corona radiata. FA was significantly reduced at the lowest level (pons), only tended to be reduced in the internal capsule, but was also unchanged in the corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports the hypothesis of a 'dying back' mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS

BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to investigate the neuronal and axonal fibre distribution in the human brain. Changes in diffusion characteristics of water molecules in the white matter can be estimated as the apparent diffusion coefficient (ADC) and the fractional anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different levels in the corticospinal tract (CST) (corona radiata, internal capsule and pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or retrograde axonal degeneration. METHODS: We studied eight ALS patients with clinical signs of upper motor neuron involvement. The patients were compared with 11 healthy age-matched controls. RESULTS: ADC was significantly increased in the CST in ALS patients at the level of the internal capsule and also increased in the pons, but without statistical significance. ADC was unchanged at the level of the corona radiata. FA was significantly reduced at the lowest level (pons), only tended to be reduced in the internal capsule, but was also unchanged in the corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports the hypothesis of a 'dying back' mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS