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1.  [No title available] 
PMCID: PMC4294185  PMID: 16511636
2.  The evolution of mild parkinsonian signs in aging 
Journal of neurology  2014;261(10):1922-1928.
The progression of mild parkinsonian signs in the absence of idiopathic Parkinson’s disease in aging is unclear. This study aims to identify predictors of the evolution of mild parkinsonian signs in non-demented older adults. Two hundred ten participants (76.25 ± 7.10 years, 57 % women) were assessed at baseline and 1-year follow-up. Mild parkinsonian signs were defined as the presence of bradykinesia, rigidity and/or rest tremor. Depending upon the presence of these features at baseline and follow-up, participants were divided into one of four groups (no, transient, persistent or new-onset mild parkinsonian signs). Physical function was assessed using gait velocity. Ninety-five participants presented with mild parkinsonian signs at baseline. At 1-year follow-up, 59 demonstrated persistent mild parkinsonian signs, while 36 recovered (i.e., transient). Participants with persistent mild parkinsonian signs were older (79.66 ± 7.15 vs. 75.81 ± 7.37 years, p = 0.01) and evidenced slower gait velocity (90.41 ± 21.46 vs. 109.92 ± 24.32 cm/s, p < 0.01) compared to those with transient mild parkinsonian signs. Gait velocity predicted persistence of mild parkinsonian signs, even after adjustments (OR: 0.96, 95 % CI: 0.94–0.98). Fifty-five participants demonstrated new-onset of mild parkinsonian signs. In comparison to participants without mild parkinsonian signs, presence of cardiovascular but not cerebrovascular disease at baseline was associated with new-onset mild parkinsonian signs. Our study reveals that gait velocity was the main predictor of persistent mild parkinsonian signs, whereas cardiovascular disease was associated with new-onset mild parkinsonian signs. These findings suggest a vascular mechanism for the onset of mild parkinsonian signs and a different mechanism, possibly neurodegenerative, for the persistence of mild parkinsonian signs.
PMCID: PMC4280073  PMID: 25047763
Mild parkinsonian signs; Aging; Gait; Cardiovascular disease; Cerebrovascular disease
3.  Clinical experience with high-dose idebenone in Friedreich ataxia 
Journal of neurology  2009;256(0 1):42-45.
Several reports in the literature describe the effects of low-dose (5 mg/kg/day) idebenone in significantly reducing cardiac hypertrophy in patients with Friedreich ataxia. However, the effects of idebenone on neurological function have not been reliably determined in these studies; when neurological parameters were reported, results were often inconclusive, usually because of subject heterogeneity and lack of adequate statistical power. In two of these studies, some patients showed beneficial effects of idebenone on their cardiomyopathy only when the dose was increased, prompting the systematic investigation of higher doses of idebenone. Following a phase 1 dose escalation study, a phase 2 tolerability and efficacy trial with low, intermediate, and high doses of idebenone was conducted. The results suggested that treatment with intermediate- and high-dose idebenone had beneficial effects on neurological symptoms. On the basis of these results, two phase 3 trials have been initiated, one in the United States with young ambulatory patients and one in Europe without limits on age and disease severity.
PMCID: PMC4277883  PMID: 19283350
Friedreich ataxia; idebenone; rare disorders; clinical trials; cardiomyopathy; neurologic; ICARS; FARS; oxidative stress
4.  [No title available] 
PMCID: PMC4289971  PMID: 25488473
5.  Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies 
Journal of neurology  2013;260(12):3115-3121.
We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound.
We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size.
Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later.
Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement.
PMCID: PMC3970398  PMID: 24101129
ultrasound; nerve; chronic inflammatory demyelinating polyneuropathy (CIDP); multifocal motor neuropathy (MMN); Charcot-Marie-Tooth (CMT); Guillain-Barre syndrome (GBS)
6.  The utility of polysomnography for the diagnosis of NREM parasomnias: an observational study over 4 years of clinical practice 
Journal of Neurology  2014;262(2):385-393.
Polysomnography (PSG) is considered the gold standard for diagnosis of non-rapid eye movement (NREM) parasomnias, however its diagnostic yield has been rarely reported. We aimed to assess the diagnostic value of polysomnography in different categories of patients with suspected NREM parasomnia and define variables that can affect the outcome. 124 adults referred for polysomnography for suspected NREM parasomnia were retrospectively identified and divided into clinical categories based on their history. Each polysomnography was analysed for features of NREM parasomnia or different sleep disorders and for presence of potential precipitants. The impact on the outcome of number of recording nights and concomitant consumption of benzodiazepines and antidepressants was assessed. Overall, PSG confirmed NREM parasomnias in 60.5 % patients and showed a different sleep disorder in another 16 %. Precipitants were found in 21 % of the 124 patients. However, PSG showed limited value when the NREM parasomnia was clinically uncomplicated, since it rarely revealed a different diagnosis or unsuspected precipitants (5 % respectively), but became essential for people with unusual features in the history where different or overlapping diagnoses (18 %) or unsuspected precipitants (24 %) were commonly identified. Taking benzodiazepines or antidepressants during the PSG reduced the diagnostic yield. PSG has a high diagnostic yield in patients with suspected NREM parasomnia, and can reveal a different diagnosis or precipitants in over 40 % of people with complicated or atypical presentation or those with a history of epilepsy. We suggest that PSG should be performed for one night in the first instance, with leg electrodes and respiratory measurements and after benzodiazepine and antidepressant withdrawal.
PMCID: PMC4330461  PMID: 25408370
Polysomnography; Sleep study; NREM parasomnias; Arousal disorders; Sleepwalking; Epilepsy
7.  Spinal cord lesions and disability in Hispanics with multiple sclerosis 
Journal of neurology  2013;260(11):10.1007/s00415-013-7054-4.
Longitudinally extensive spinal cord lesions (LESCLs) are believed to occur predominantly with opticospinal multiple sclerosis (OSMS) and are associated with disability.
To describe the prevalence and patterns of spinal cord lesions in Hispanics with multiple sclerosis (MS) and OSMS and their association with disability.
Cross-sectional study of 164 patients with complete MRIs. Spinal cord was classified: LESCLs, scattered spinal cord lesions (sSCLs) or no spinal cord lesions (noSCLs). Clinical course was defined as classical MS or OSMS. Risk of disability (Expanded Disability Status Scale ≥4.0) was adjusted for age, disease duration and sex using logistic regression.
125/164(73%) MS patients had spinal cord lesions (sSCLs, 57%; LESCLs, 19%) but only 11(7%) had OSMS. LESCLs were associated with disability (p<0.0001), longer disease duration (p<0.0001) and MS (n=21 vs. n=10 OSMS; p<0.0001). LESCLs was associated with the greatest risk to disability (OR 7.3, 95% CIs1.9-26.5; p=0.003; sSCLs OR 2.5, 95% CIs0.9-7.1; p=0.09) compared with noSCLs.
LESCLs are more common than OSMS and are associated with worse disability even in patients with MS. These results suggest that LESCLs are a more important marker of disability in MS than OSMS and may be an early indicator of more aggressive disease in this population.
PMCID: PMC3816004  PMID: 23912723
Multiple sclerosis; opticospinal; spinal cord; Hispanic; Asian
8.  [No title available] 
PMCID: PMC4289978  PMID: 25344746
9.  Heinrich Sachs (1863–1928) 
Journal of Neurology  2014;262(2):498-500.
PMCID: PMC4330404  PMID: 25344744
10.  Oligoclonal bands in the cerebrospinal fluid of amyotrophic lateral sclerosis patients with disease-associated mutations 
Journal of neurology  2012;260(1):85-92.
In amyotrophic lateral sclerosis (ALS) cerebrospinal fluid (CSF) analysis is usually performed to exclude inflammatory processes of the central nervous system. Although in a small subset of patients an intrathecal synthesis of IgG is detectable, usually there is no clear explanation for this evidence. This study investigates the occurrence of oligoclonal bands (OCBs) in the CSF of a large series of ALS patients, attempting a correlation with genotype data. CSF was collected from 259 ALS patients. CSF parameters were measured according to standard procedures, and detection of OCBs performed by isoelectric focusing. The patients were screened for mutations in SOD1, FUS, TARDBP, ANG, OPTN, and C9ORF72. We observed the presence of OCBs in the CSF of 9/259 ALS patients (3.5 %), and of disease-associated mutations in 12 cases. OCBs were significantly more frequent in mutation carriers compared to the remaining cohort (3/12 vs 6/247; p < 0.01). Among patients with OCBs, two patients had the TARDBP p.A382T mutation (one of which in homozygous state), and one the ANG p.P-4S variant. Both patients carrying the p.A382T mutation had an atypical phenotype, one of them manifesting signs suggestive of a cerebellar involvement, and the other presenting neuroradiological findings suggestive of an inflammatory disorder of the central nervous system. Our results suggest that ALS patients with OCBs may harbor mutations in disease-causing genes. We speculate that mutations in both TARDBP and ANG genes may disrupt the blood–brain barrier (BBB), promoting local immune responses and neuroinflammation. The role of mutant TARDBP and ANG genes on BBB integrity of ALS patients warrants further investigation.
PMCID: PMC4196642  PMID: 22752089
ALS; Genetics; Neuroimmunology; CSF; Motor neuron disease
13.  Memory Impairment in Multiple Sclerosis is Due to a Core Deficit in Initial Learning 
Journal of neurology  2013;260(10):2491-2496.
Persons with multiple sclerosis (MS) suffer memory impairment, but research on the nature of MS-related memory problems is mixed. Some have argued for a core deficit in retrieval, while others have identified deficient initial learning as the core deficit. We used a selective reminding paradigm to determine whether deficient initial learning or delayed retrieval represents the primary memory deficit in 44 persons with MS. Brain atrophy was measured from high-resolution MRIs. Regression analyses examined the impact of brain atrophy on (a) initial learning and delayed retrieval separately, and then (b) delayed retrieval controlling for initial learning. Brain atrophy was negatively associated with both initial learning and delayed retrieval (ps < .01), but brain atrophy was unrelated to retrieval when controlling for initial learning (p > .05). In addition, brain atrophy was associated with inefficient learning across initial acquisition trials, and brain atrophy was unrelated to delayed recall among MS subjects who successfully acquired the word list (although such learning frequently required many exposures). Taken together, memory deficits in MS are a result of deficits in initial learning; moreover, initial learning mediates the relationship between brain atrophy and subsequent retrieval, thereby supporting the core learning-deficit hypothesis of memory impairment in MS.
PMCID: PMC3796043  PMID: 23832311
Multiple Sclerosis; Learning; Memory; Neuropsychology; Cognitive Disorders; Atrophy
14.  An adult-onset leukoencephalopathy with axonal spheroids and pigmented glia accompanied by brain calcifications 
Journal of neurology  2013;260(10):10.1007/s00415-013-7093-x.
PMCID: PMC3865925  PMID: 24036850
adult-onset leukoencephalopathy with axonal spheroids and pigmented glia; CSF1R; calcification; computed tomography; white matter; differential diagnosis
15.  Diagnostic Odyssey of Patients with Myotonic Dystrophy 
Journal of neurology  2013;260(10):2497-2504.
The onset and symptoms of the myotonic dystrophies are diverse, complicating their diagnoses and limiting a comprehensive approach to their clinical care. This report analyzes the diagnostic delay (time from onset of first symptom to diagnosis) in a large sample of myotonic dystrophy (DM) patients enrolled in the US National Registry [679 DM type 1 (DM1) and 135 DM type 2 (DM2) patients]. Age of onset averaged 34.0 ± 14.1 years in DM2 patients compared to 26.1 ± 13.2 years in DM1 (p<0.0001). The most common initial symptom in DM2 patients was leg weakness (32.6%) compared to grip myotonia in DM1 (38.3%). Pain was reported as the first symptom in 11.1% of DM2 and 3.0% of DM1 patients (p<0.0001). Reaching the correct diagnosis in DM2 took 14 years on average (double the time compared to DM1) and a significantly higher percentage of patients underwent extended workup including electromyography, muscle biopsies, and finally genetic testing. DM patients who were index cases experienced similar diagnostic delays to non-index cases of DM. Further evaluation of how to shorten these diagnostic delays and limit their impact on burdens of disease, family planning, and symptom management is needed.
PMCID: PMC4162528  PMID: 23807151
myotonic dystrophy; facioscapulohumeral muscular dystrophy; registry; muscular dystrophy; clinical care guidelines
16.  Magnetization transfer ratio in the delayed-release dimethyl fumarate DEFINE study 
Journal of Neurology  2014;261(12):2429-2437.
We measured changes in brain magnetization transfer ratio (MTR) as a potential indicator of myelin density in brain tissue of patients with relapsing-remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) in the Phase 3 DEFINE study. DEFINE was a randomized, double-blind, placebo-controlled study in which patients with RRMS were randomized 1:1:1 to 2 years of treatment with delayed-release DMF 240 mg twice daily (BID) or three times daily (TID) or placebo. MTR was analyzed in whole brain and normal-appearing brain tissue (NABT) at baseline, week 24, 1 year, and 2 years in a subset of patients. MTR data from 392 patients were analyzed. Mean percentage reduction from baseline to 2 years in median whole brain MTR was −0.386 % in the placebo group vs increases of 0.129 % (p = 0.0027) and 0.096 % (p = 0.0051) in the delayed-release DMF BID and TID groups, respectively. Similarly, mean percentage reduction from baseline in median NABT MTR was −0.392 % with placebo vs increases of 0.190 % (p = 0.0006) and 0.115 % (p = 0.0029) with delayed-release DMF BID and TID, respectively. Post hoc analysis of data from patients with no new or enlarging T2 lesions (n = 147), or who experienced no relapses (n = 238), yielded similar results. In this analysis, increases in MTR in brain tissue most likely reflect increases in myelin density in response to delayed-release DMF. These data in patients with RRMS are consistent with preclinical studies that indicate a potential for cytoprotection and remyelination with delayed-release DMF treatment.
Electronic supplementary material
The online version of this article (doi:10.1007/s00415-014-7504-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4242981  PMID: 25270680
Delayed-release dimethyl fumarate; Magnetic resonance imaging; Magnetization transfer ratio; Multiple sclerosis
18.  Multidisciplinary treatment for functional neurological symptoms: a prospective study 
Journal of Neurology  2014;261(12):2370-2377.
Although functional neurological symptoms are often very disabling there is limited information on outcome after treatment. Here we prospectively assessed the short- and long-term efficacy of an inpatient multidisciplinary programme for patients with FNS. We also sought to determine predictors of good outcome by assessing the responsiveness of different scales administered at admission, discharge and follow-up. Sixty-six consecutive patients were included. Assessments at admission, discharge and at 1 year follow-up (55 %) included: the Health of the Nation Outcome Scale, the Hospital Anxiety and Depression Scale, the Patient Health Questionnaire-15, the Revised Illness Perception Questionnaire, the Common Neurological Symptom Questionnaire, the Fear Questionnaire and the Canadian Occupational Performance Measure. At discharge and at 1 year follow-up patients were also asked to complete five-point self-rated scales of improvement. There were significant improvements in clinician-rated mental health and functional ability. In addition, patients reported that their levels of mood and anxiety had improved and that they were less bothered by somatic symptoms in general and neurological symptoms in particular. Two-thirds of patients rated their general health such as “better” or “much better” at discharge and this improvement was maintained over the following year. Change in HoNOS score was the only measure that successfully predicted patient-rated improvement. Our data suggest that a specialized multidisciplinary inpatient programme for FNS can provide long-lasting benefits in the majority of patients. Good outcome at discharge was exclusively predicted by improvement in the HoNOS which continued to improve over the 1 year following discharge.
PMCID: PMC4242999  PMID: 25239392
Functional neurological symptoms; Psychogenic neurological symptoms; Conversion disorders; Inpatient programme; Psychotherapy; Physiotherapy
20.  Overview of neurosarcoidosis: recent advances 
Journal of Neurology  2014;262(2):258-267.
Sarcoidosis (SA) is a granulomatous, multisystem disease of unknown etiology. Most often the disease affects lungs and mediastinal lymph nodes, but it may occur in other organs. Neurosarcoidosis (NS) more commonly occurs with other sarcoidosis forms, in 1 % of cases it involves only nervous system. Symptomatic NS occurs but on autopsy study up to 25 % of cases are confirmed. NS can affect central nervous system: the brain, spinal cord and peripheral nerves, and muscles. The diagnosis of neurosarcoidosis facilitates diagnostic criteria: histopathological, imaging and cerebrospinal fluid examination, and clinical symptoms. At present, there are no set standards for treatment of patients suffering from NS. Early therapy of symptomatic patients is recommended. Corticosteroids still are the first line of treatment for NS patients. In cases of steroids resistance, lack of their effectiveness or existence of contraindication to their use, immunosuppressant treatment is recommended. The latest NS algorithm with immunosuppressive treatment is discussed.
PMCID: PMC4330460  PMID: 25194844
Neurosarcoidosis; Neurosarcoidosis forms; Clinical symptoms; Diagnosis; Treatment
21.  ANO10 mutations cause ataxia and coenzyme Q10 deficiency 
Journal of Neurology  2014;261(11):2192-2198.
Inherited ataxias are heterogeneous disorders affecting both children and adults, with over 40 different causative genes, making molecular genetic diagnosis challenging. Although recent advances in next-generation sequencing have significantly improved mutation detection, few treatments exist for patients with inherited ataxia. In two patients with adult-onset cerebellar ataxia and coenzyme Q10 (CoQ10) deficiency in muscle, whole exome sequencing revealed mutations in ANO10, which encodes anoctamin 10, a member of a family of putative calcium-activated chloride channels, and the causative gene for autosomal recessive spinocerebellar ataxia-10 (SCAR10). Both patients presented with slowly progressive ataxia and dysarthria leading to severe disability in the sixth decade. Epilepsy and learning difficulties were also present in one patient, while retinal degeneration and cataract were present in the other. The detection of mutations in ANO10 in our patients indicate that ANO10 defects cause secondary low CoQ10 and SCAR10 patients may benefit from CoQ10 supplementation.
Electronic supplementary material
The online version of this article (doi:10.1007/s00415-014-7476-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4221650  PMID: 25182700
Autosomal recessive ataxia; Mitochondrial; Coenzyme Q10 (CoQ10) deficiency; ANO10
22.  The genetics of ataxia: through the labyrinth of the Minotaur, looking for Ariadne’s thread 
Journal of Neurology  2014;261(Suppl 2):528-541.
Among the hereditary cerebellar ataxias (CAs), there are at least 36 different forms of autosomal dominant cerebellar ataxia (ADCAs), 20 autosomal recessive cerebellar ataxias (ARCAs), two X-linked ataxias, and several forms of ataxia associated with mitochondrial defects. Despite the steady increase in the number of newly discovered CA genes, patients, especially those with putative ARCAs, cannot yet be genotyped. Moreover, in daily clinical practice, ataxia may present as an isolated cerebellar syndrome or, more often, it is associated with a broad spectrum of neurological manifestations including pyramidal, extrapyramidal, sensory, and cognitive dysfunction. Furthermore, non-neurological symptoms may also coexist. A close integration between clinical records, neurophysiological, neuroradiological and, in some instances, biochemical findings will help physicians in the diagnostic work-up (including selection of the correct genetic tests) and may lead to timely therapy. Some inherited CAs are in fact potentially treatable, and the efficacy of the therapy is directly related to the severity of the cerebellar atrophy and to the time of onset of the disease. Most cases of CA are sporadic, and the diagnostic work-up remains a challenge. Detailed anamnesis and deep investigation of the family pedigree are usually enough to discriminate between acquired and genetic conditions. In the case of ADCA, molecular testing should be guided by taking into account the main associated symptoms. In sporadic cases, a multi-disciplinary approach is needed and should consider the following points: (1) onset and clinical course; (2) associated features; (3) neurophysiological parameters, with special attention to the occurrence of peripheral neuropathy; (4) neuroimaging results; and (5) laboratory findings. A late-onset sporadic ataxia, in which other possible causes have been excluded by following the proposed steps, might be attributable to metabolic disorders, which in some instances may be treatable. In this review, we will guide the reader through the labyrinth of CAs, and we propose a diagnostic flow chart.
PMCID: PMC4141148  PMID: 25145890
Ataxia; Cerebellum; Diagnosis; Genes; Metabolism
23.  Niemann–Pick disease type C: introduction and main clinical features 
Journal of Neurology  2014;261(Suppl 2):525-527.
PMCID: PMC4141151  PMID: 25145889
24.  Central ocular motor disorders, including gaze palsy and nystagmus 
Journal of Neurology  2014;261(Suppl 2):542-558.
An impairment of eye movements, or nystagmus, is seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum, as well as in those of the vestibular system. The key to diagnosis is a systematic clinical examination of the different types of eye movements, including: eye position, range of eye movements, smooth pursuit, saccades, gaze-holding function and optokinetic nystagmus, as well as testing for the different types of nystagmus (e.g., central fixation nystagmus or peripheral vestibular nystagmus). Depending on the time course of the signs and symptoms, eye movements often indicate a specific underlying cause (e.g., stroke or neurodegenerative or metabolic disorders). A detailed knowledge of the anatomy and physiology of eye movements enables the physician to localize the disturbance to a specific area in the brainstem (midbrain, pons or medulla) or cerebellum (in particular the flocculus). For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fascicle, with impaired vertical saccades only, the interstitial nucleus of Cajal or the posterior commissure; common causes with an acute onset are an infarction or bleeding in the upper midbrain or in patients with chronic progressive supranuclear palsy (PSP) and Niemann–Pick type C (NP-C). Isolated dysfunction of horizontal saccades is due to a pontine lesion affecting the paramedian pontine reticular formation due, for instance, to brainstem bleeding, glioma or Gaucher disease type 3; an impairment of horizontal and vertical saccades is found in later stages of PSP, NP-C and Gaucher disease type 3. Gaze-evoked nystagmus (GEN) in all directions indicates a cerebellar dysfunction and can have multiple causes such as drugs, in particular antiepileptics, chronic alcohol abuse, neurodegenerative cerebellar disorders or cerebellar ataxias; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule. The most common pathological types of central nystagmus are downbeat nystagmus (DBN) and upbeat nystagmus (UBN). DBN is generally due to cerebellar dysfunction affecting the flocculus bilaterally (e.g., due to a neurodegenerative disease). Treatment options exist for a few disorders: miglustat for NP-C and aminopyridines for DBN and UBN. It is therefore particularly important to identify treatable cases with these conditions.
PMCID: PMC4141156  PMID: 25145891
Ocular motor; Examination; Neurodegenerative disorder; Diagnosis; Treatment
25.  Psychiatric signs and symptoms in treatable inborn errors of metabolism 
Journal of Neurology  2014;261(Suppl 2):559-568.
Possible underlying organic causes of psychiatric symptoms can be overlooked in the clinical setting. It is important to increase awareness amongst psychiatric and neurological professionals with regard to certain inborn errors of metabolism as, in some cases, disease-specific therapies are available that can, for instance, treat underlying metabolic causes. The following article describes the basic pathophysiology, clinical and neurological features, and available diagnostic procedures of six treatable metabolic diseases that are associated with neuropsychiatric symptoms: Wilson’s disease, cerebrotendinous xanthomatosis, porphyrias, homocysteinemia, urea cycle disorders, and Niemann-Pick disease type C (NP-C). NP-C is taken as a particularly relevant example because, while it is traditionally considered to be a condition that presents with severe neurological and systemic manifestations in children, an increasing number of patients are being detected who have the adolescent- or adult-onset form, which is frequently associated with neuropsychiatric signs. A notable proportion of adult-onset cases have been reported where NP-C has mistakenly been diagnosed and treated as a psychiatric condition, usually based on patients’ initial presentation with psychotic or schizophrenia-like symptoms. Underlying organic causes of psychiatric disorders such as psychosis should be considered among patients with atypical symptoms and/or resistance to standard therapy. Alongside improved frameworks for additional multidisciplinary diagnostic work in patients with suspected organic disease, the development of convenient and affordable biochemical screening and/or diagnostic methods has enabled new ways to narrow down differential diagnoses.
PMCID: PMC4141145  PMID: 25145892
Organic psychosis; Diagnosis; Psychosis; Cognitive impairment; Niemann-Pick disease type C; Metachromatic leukodystrophy

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