Case 17: Sudden Paralysis in a Boy With Headaches An adolescent boy with chronic headaches presents with episodes of "legs giving out." Are the 2 symptoms linked? Clinical Case, July 18, 2007
Case 16: Chasing the Dragon After a 2- to 3-day drinking binge, this young man suffered a relentless deterioration in his mental status. What caused his fulminant coma? Clinical Case, April 18, 2007
Case 15: When a Stroke Is Not a Stroke A patient with AIDS presents with strokelike symptoms. Can you find the underlying cause? Clinical Case, January 30, 2007
Case 13: A Man With Progressive Headache and Confusion What "red flags" point to the need to search for serious underlying mechanisms of headache? What is the differential for pachymeningeal enhancement? Test yourself and learn with this interactive case. Clinical Case, July 26, 2006
Case 12: My Doctor Says That I Have ALS! The patient had a "funny feeling" in his right leg and an EMG suspicious for ALS, but his history and symptoms didn't quite add up. Can you make the correct diagnosis? Clinical Case, March 22, 2006
Case 11: A Young Woman With Ring-Enhancing Brain Lesions Learn about the case of a 35-year-old woman who presented with blurred vision associated with headache and left-side numbness. Clinical Case, January 05, 2006
Case 10: It's "The Vision Thing" Learn about the diagnosis, prognosis, and treatment of this patient who was admitted to the hospital with a complaint of "I can't see." Clinical Case, July 26, 2005
Pregnant? Who's Pregnant?: Memory Loss in a Young Woman The patient is a 19-year-old pregnant woman with a history of cystic fibrosis, Graves' disease, acquired hearing loss, and CF-related diabetes, who presents to the hospital after being "found down." Clinical Case, May 26, 2005
Case 8: Absentminded and "Walking Like a Drunk" Test your diagnostic skills in this Johns Hopkins Clinical Case: A 58-year-old man with no significant past medical history experienced rapidly progressive neurologic symptoms. Clinical Case, February 03, 2005
Case 7: Chief Complaint: Paraplegia and Encephalopathy Test your diagnostic skills with this challenging interactive case study from Johns Hopkins. Journal Article, December 15, 2004
Case 6: When Is a Headache Not Just a Headache? A 41-year-old healthy woman underwent a gingival scraping procedure. Following the procedure, she developed fever and malaise, and the "worst headache of her life." Clinical Case, July 01, 2004
Altered Mental Status, Fever After Resection of Glioblastoma A 54-year-old man with a medical history of hypertension presented to the emergency room after a single, generalized tonic-clonic seizure. Clinical Case, April 08, 2004
Case 4: Just a Bruise? A 20-month-old girl presents to the emergency department after falling from her couch, hitting her head on a coffee table, and then becoming sleepy. Clinical Case, November 24, 2003
44-Year-Old Man With Fever, Headache, Confusion, and Ataxia A man from India with a 2-month history of low-grade fever, headache, and neck pain presents with gradual worsening of symptoms. His medical history is remarkable for uveitis for 2 years prior. Journal Article, August 28, 2003
Case 2: Acute Ascending Paralysis in a 4-Year-Old Boy A "limp" rapidly progresses to generalized weakness Journal Article, April 10, 2003
Case 1: A Woman With Headache and Dizziness This patient worsened despite treatment. What's your diagnosis? Clinical Case, February 14, 2003
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Revising a diagnosis of functional neurological disorder—a case report
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Alex J Berry, Sarah Wiethoff, Revising a diagnosis of functional neurological disorder—a case report, Oxford Medical Case Reports , Volume 2020, Issue 9, September 2020, omaa073, https://doi.org/10.1093/omcr/omaa073
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We report a case of a 62-year-old female diagnosed with functional neurological disorder (FND), where the diagnosis was eventually revised to progressive supranuclear palsy 3 years after symptom onset. FND is a commonly encountered condition and can be diagnosed with a considerable degree of confidence in most cases. FND is associated with significant functional impairment and may occur alongside other neurological disorders, and there is now a growing evidence base for symptom-specific FND treatments. Charting clinical progression of symptoms and serial neuroimaging were useful in refining the diagnosis in this case. Alhough the diagnosis was ultimately revised to a neurodegenerative disorder, a degree of functional overlay likely remained present. The case highlights the importance of recognizing and avoiding diagnostic overshadowing in those with FND.
Functional neurological disorders (FND) are defined by neurological symptoms not explained by identifiable neurological pathology and represent up to one-third of neurology outpatient clinic attendances [ 1 ]. There is growing emphasis on diagnosis involving demonstration of positive clinical signs (e.g. Hoover’s sign), and a reduced emphasis on the demonstration of precipitating traumatic life-events (though adverse life events appear consistently overrepresented in FND patients compared to the general population) [ 1 , 2 ]. FND diagnoses demonstrate high diagnostic stability, with a misdiagnosis rate of 4% according to one systematic review [ 3 ].
We report a case where an FND diagnosis was revised to that of a neurodegenerative disorder, 3 years after symptom onset.
A 62-year-old female presented to neuropsychiatry services with a 3-year history of gradually progressive dysphonia, difficulty with keeping her eyes open and falls.
Her medical history consisted of chronic obstructive pulmonary disease, type 2 diabetes mellitus, ischaemic heart disease, hypertension, grade 3b chronic kidney disease (secondary to hypertensive disease) and anaemia. There was no personal or family history of medical or psychiatric disease, other than her mother having had a brain tumour in her 60s. She was married and unemployed. She has two siblings and 2 daughters; all of whom are well.
She was referred to otorhinolaryngology 1 year after the development of vocal symptoms. At the time, there was no associated odynophagia or dysphagia, but she had described all-over-body pain and difficulty with handwriting. She started experiencing difficulty keeping her eyes open voluntarily and found wearing sunglasses helped with this. Laryngoscopy revealed slowed movements of the hypopharynx and larynx. Speech and language therapy (SALT) assessment reported normal orofacial muscle function with effortful and delayed vocal production. Communication was often supplemented with hand gestures. She was referred to neurology for further opinion. Neurological examination reported as being normal apart from speech. Vocal output was variable, at times able to produce complete words audibly, at other times being unable to phonate or imitate sounds to command. She was able to cough and swallowing was preserved. Magnetic resonance imaging (MRI) at the time revealed no abnormalities ( Fig. 1 ). A diagnosis of functional voice disorder was made, and she was referred to an inpatient rehabilitation programme for patients with FND.
T2-weighted MRI scan showing normal appearances 1 year after symptom onset.
Neuropsychiatric review (3 years after symptom onset) revealed that she had started falling and stopped cooking or going outdoors (though she denied affective symptoms). Montreal Cognitive Assessment revealed a score of 22/30. Neurological examination demonstrated aphonia, eyelid apraxia and blepharospasm, near-constant use of sunglasses indoors and frequent touching of the corner of her eyes (a sensory geste).
MRI showed normal midbrain and pontine volumes, with hypointense signal within the substantia nigra, red nuclei and globus pallidus on susceptibility-weighted imaging (SWI), suggestive of iron deposition ( Fig. 2 ). Computed tomography showed no evidence of intracerebral calcification. The diagnosis was then revised from FND to an atypical akinetic rigid syndrome. Gait speed and efficiency had improved at the point of discharge from the rehabilitation programme, which was felt to be a non-specific effect of physiotherapy.
Susceptibility-weighted MRI scan showing hypointense signal within the bilateral globi pallidi, 3 years after symptom onset.
Her care was then transferred to neurology. Clinical examination revealed aphonia and apraxia of eyelid opening, mild limitation of upgaze, hypometric vertical saccades and frontalis overactivity. Bilateral bradykinesia, right-sided rigidity and right foot dystonia also were noted. A summary of investigation findings is shown in Table 1 , including genetic testing for atypical Parkinsonian syndromes associated with brain iron-deposition, and a DaTScan ( Fig. 3 ). A clinical diagnosis of progressive supranuclear palsy was made, and she received ongoing botulinum toxin treatment and SALT input.
Summary of investigations: normal values are within brackets.
Investigation .
Results .
Full blood count
Haemoglobin 103 (115–155 g/L), haematocrit 0.329 (0.33–45 L/L), mean corpuscular haemoglobin 313 (320–360 g/L), mean corpuscular volume 103.1 (80–99 fL), white cell count and platelets within normal ranges
Renal function
eGFR 34 ml/min, creatinine 140 (49–92 μmol/L), urea 17.7 mmol/L, sodium and potassium within normal limits
Liver function tests
Alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and albumin within normal ranges
Iron studies
Ferritin 306 μg/L (13–150 μg/L), iron 12.8 (6.6–26 μmol/L), total iron-binding capacity 58 (41–77 μmol/L), iron-binding saturation 22% (15–50%)
Caeruloplasmin
0.22 g/L (normal range 0.16–0.45 g/L)
MRI brain
Hypointensity of the substantia nigra, red nuclei and globus pallidus on SWI sequence
CT head
No intracerebral calcification
DaTscan
Marked reduction in tracer binding bilaterally
Electromyography and electroencephalography
Subcortical negative myoclonus and polyminimyoclonus when attempting to flex upper limbs against force
Autonomic testing
Normal basal plasma catecholamines, no evidence of cardiovascular failure, and preserved responses to cold
Genetic testing
No pathogenic mutations identified within the following:
Neuropsychometric testing
Slowed performances on tests of attention and processing speed, suggesting mild anterior and subcortical dysfunction
Investigation .
Results .
Full blood count
Haemoglobin 103 (115–155 g/L), haematocrit 0.329 (0.33–45 L/L), mean corpuscular haemoglobin 313 (320–360 g/L), mean corpuscular volume 103.1 (80–99 fL), white cell count and platelets within normal ranges
Renal function
eGFR 34 ml/min, creatinine 140 (49–92 μmol/L), urea 17.7 mmol/L, sodium and potassium within normal limits
Liver function tests
Alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and albumin within normal ranges
Iron studies
Ferritin 306 μg/L (13–150 μg/L), iron 12.8 (6.6–26 μmol/L), total iron-binding capacity 58 (41–77 μmol/L), iron-binding saturation 22% (15–50%)
Caeruloplasmin
0.22 g/L (normal range 0.16–0.45 g/L)
MRI brain
Hypointensity of the substantia nigra, red nuclei and globus pallidus on SWI sequence
CT head
No intracerebral calcification
DaTscan
Marked reduction in tracer binding bilaterally
Electromyography and electroencephalography
Subcortical negative myoclonus and polyminimyoclonus when attempting to flex upper limbs against force
Autonomic testing
Normal basal plasma catecholamines, no evidence of cardiovascular failure, and preserved responses to cold
Genetic testing
No pathogenic mutations identified within the following:
Neuropsychometric testing
Slowed performances on tests of attention and processing speed, suggesting mild anterior and subcortical dysfunction
DaTscan results showing reduced [ 123 I] FPCIT tracer uptake bilaterally, 3 years after symptom onset.
Her mobility and speech partially responded to levodopa treatment, and eyelid apraxia was partially responsive to botulinum toxin administered to the orbicularis oculi. Laryngeal botulinum toxin treatment was considered, but not used due to potential risk of aspiration. It was notable that SALT continued to identify features suggestive of an additional functional component to her phonation difficulties, where speech appeared to reliably worsen during times of testing and improved with distraction. Breath-holding during speech was particularly prominent, though she was noted to be able to demonstrate an ability for free breath-flow during non-speech tasks.
PSP is a 4-repeat tauopathy, characterized clinically by gait-disturbance, Parkinsonian features, impaired ocular movement, neuropsychiatric changes, dysarthria and falls. Significant clinical heterogeneity amongst neuropathologically confirmed PSP cases has been increasingly recognzed, including a phenotype characterized with non-fluent primary progressive aphasia and apraxia of speech [ 4 ].
Basal ganglia iron deposition has been described in PSP, with hypointensities of the red nucleus and globi pallidi on susceptibility-weighted MRI showing some value in discriminating PSP from other Parkinson-plus syndromes [ 5 ]. Neurodegeneration with brain-iron accumulation, a range of inherited disorders characterized by abnormal brain iron deposition were considered as potential differential diagnoses—with special emphasis on aceruloplasminemia in light of the age-at-onset, raised serum ferritin, radiological evidence of red nucleus involvement and the presence of type-2 diabetes mellitus [ 6 ]. However, normal serum ceruloplasmin concentration and negative ceruloplasmin gene ( CP ) genetic testing ruled out aceruloplasminemia.
Functional voice disorders are typically characterized by exaggerated lip, tongue and respiratory movements during phonation (which may resemble apraxia of speech), a waxing-and-waning pattern of speech disturbance and demonstrable inconsistencies (e.g. the voice may normalize during non-propositional speech or singing, laughing or coughing may be preserved, or normal vocal cord movement may be demonstrable on laryngoscopy) [ 7 ]. Treatment includes addressing psychosocial stressors and may involve cognitive-behavioural or family therapy-orientated approaches. The presence of an element of distractibility in this case may suggest functional ‘overlay’ (where functional symptoms present alongside a separate disorder). Whilst we cannot exclude confirmation bias from the SALT assessments, it is notable that multiple SALT therapists remarked on the presence of persisting functional-overlay, even after the diagnosis was revised to PSP. FND may be precipitated by the development of separate neurological disorders, or other psychosocial or physiological insults, though the mechanism underlying this association remains unclear [ 8 ].
‘Diagnostic overshadowing’ refers to the misattribution of physical symptoms or signs to psychiatric conditions, which likely occurred in this case. For example, the indoor use of sunglasses (which has been associated with FND [ 9 ]) was misinterpreted as a sign of FND (in this case, sunglasses were used to prevent aggravation of blepharospasm) by a number of clinicians reviewing the patient following the initial diagnosis of FND. Though a preserved cough was noted in this case, we speculate that the acoustics may have been altered by the presence of upper airway mucus from COPD, raising the possibility of a false-positive sign (a ‘falsely-loud’ cough). The observation of hypokinetic movements on laryngoscopy is unlikely to be explained by FND and highlights the importance of a thorough review of historic investigations in cases where FND diagnoses have been considered.
Clinicians may encounter considerable psychological resistance from patients when attempting to revise a previous diagnosis to an FND diagnosis. Patients may similarly encounter psychological resistance from clinicians when attempting to argue their FND diagnosis should be revised to a structural neurological disorder. Interestingly, revising the diagnosis from FND to a neurodegenerative disorder was not met with resistance in this case, in spite of the arguably worse prognosis associated with PSP. Whilst neuropsychometric testing did not reveal gross cognitive impairment, it is possible a degree of alexithymia may have accounted for this (though this was not formally assessed) [ 10 ].
Conflict of interest statement . None declared.
S.W. is supported by the Ministry of Science, Research and the Arts of Baden-Württemberg and the European Social Fund of Baden-Württemberg (31-7635 41/67/1).
Ethical approval not required (available at request).
Patient consent obtained in written form.
Dr Alex J. Berry.
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Case Study 1: A 55-Year-Old Woman With Progressive Cognitive, Perceptual, and Motor Impairments
Information & authors, metrics & citations, view options, case presentation, what are diagnostic considerations based on the history how might a clinical examination help to narrow the differential diagnosis.
How Does the Examination Contribute to Our Understanding of Diagnostic Considerations? What Additional Tests or Studies Are Indicated?
Feature
Posterior cortical atrophy
Corticobasal syndrome
Cognitive and motor features
Visual-perceptual: space perception deficit, simultanagnosia, object perception deficit, environmental agnosia, alexia, apperceptive prosopagnosia, and homonymous visual field defect
Motor: limb rigidity or akinesia, limb dystonia, and limb myoclonus
Visual-motor: constructional dyspraxia, oculomotor apraxia, optic ataxia, and dressing apraxia
Other: left/right disorientation, acalculia, limb apraxia, agraphia, and finger agnosia
Higher cortical features: limb or orobuccal apraxia, cortical sensory deficit, and alien limb phenomena
Imaging features (MRI, FDG-PET, SPECT)
Predominant occipito-parietal or occipito-temporal atrophy, and hypometabolism or hypoperfusion
Asymmetric perirolandic, posterior frontal, parietal atrophy, and hypometabolism or hypoperfusion
Neuropathological associations
AD>CBD, LBD, TDP, JCD
CBD>PSP, AD, TDP
Considering This Additional Data, What Would Be an Appropriate Diagnostic Formulation?
Does information about the longitudinal course of her illness alter the formulation about the most likely underlying neuropathological process, neuropathology.
Feature
Case of PCA/CBS due to AD
Exemplar case of CBD
Macroscopic findings
Cortical atrophy: symmetric, mild
Cortical atrophy: often asymmetric, predominantly affecting perirolandic cortex
Substantia nigra: appropriately pigmented
Substantia nigra: severely depigmented
Microscopic findings
Tau neurofibrillary tangles and beta-amyloid plaques
Primary tauopathy
No tau pathology in white matter
Tau pathology involves white matter
Hirano bodies, granulovacuolar degeneration
Ballooned neurons, astrocytic plaques, and oligodendroglial coiled bodies
(Lewy bodies, limbic)
Information
Published in.
Posterior Cortical Atrophy
Corticobasal Syndrome
Atypical Alzheimer Disease
Network Degeneration
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Neurology Case Studies: Cerebrovascular Disease
Affiliations.
1 Division of Stroke and Vascular Neurology, Mercy Health Hauenstein Neurosciences, 200 Jefferson Street Southeast, Grand Rapids, MI 49503, USA. Electronic address: [email protected].
2 Department Translational Science & Molecular Medicine, Mercy Health Hauenstein Neurosciences, Michigan State University College of Human Medicine, 220 Cherry Street Southeast, Room H 3037, Grand Rapids, MI 49503, USA.
PMID: 27445238
DOI: 10.1016/j.ncl.2016.04.001
This article discusses interesting vascular neurology cases including the management of intracranial stenosis, migraine headache and stroke risk, retinal artery occlusions associated with impaired hearing, intracranial occlusive disease, a heritable cause of stroke and vascular cognitive impairment, and an interesting clinico-neuroradiologic disorder associated with eclampsia.
The relationship of migraine and stroke. Tietjen GE. Tietjen GE. Neuroepidemiology. 2000 Jan-Feb;19(1):13-9. doi: 10.1159/000026233. Neuroepidemiology. 2000. PMID: 10654284 Review.
[Cerebrovascular accidents and migraine]. Castaigne P, Brunet P, Pierrot-Deseilligny C, Roullet E. Castaigne P, et al. Ann Med Interne (Paris). 1983;134(4):306-9. Ann Med Interne (Paris). 1983. PMID: 6614710 French.
Stroke, migraine and intracranial aneurysm: a case report. Mas JL, Baron JC, Bousser MG, Chiras J. Mas JL, et al. Stroke. 1986 Sep-Oct;17(5):1019-21. doi: 10.1161/01.str.17.5.1019. Stroke. 1986. PMID: 3764946
Stroke and migraine in the Oxfordshire Community Stroke Project. Henrich JB, Sandercock PA, Warlow CP, Jones LN. Henrich JB, et al. J Neurol. 1986 Oct;233(5):257-62. doi: 10.1007/BF00314155. J Neurol. 1986. PMID: 3772405
Migraine-related stroke in the context of the International Headache Society classification of head pain. Welch KM, Levine SR. Welch KM, et al. Arch Neurol. 1990 Apr;47(4):458-62. doi: 10.1001/archneur.1990.00530040114027. Arch Neurol. 1990. PMID: 2181979 Review.
Management of blood pressure in stroke. Gorelick PB, Qureshi S, Farooq MU. Gorelick PB, et al. Int J Cardiol Hypertens. 2019 Oct 13;3:100021. doi: 10.1016/j.ijchy.2019.100021. eCollection 2019 Nov. Int J Cardiol Hypertens. 2019. PMID: 33447751 Free PMC article. Review.
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Case Reports in Neurology
About the journal, aims and scope, journal sections.
Single Case- General Neurology
Single Case- Headache
Case Series- General Neurology
Case Series- Headache
Article Types
Case report.
A downloadable template is available below.
Case Report (DOCX, 33 KB)
Case reports should contain up to 2,500 words, up to 3 illustrations, 2 tables, a maximum of 15 references and an abstract of no more than 250 words.
We require that authors provide a completed CARE checklist when submitting a Case Report. Submissions without this may be returned to the author as incomplete.
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Editorial and Journal Policies
Getting started.
When preparing a manuscript, it is important to review the editorial policies. For full details, please visit the Publication Ethics and Editorial Policies page. Karger Publishers is a member of the Committee on Publication Ethics (COPE). Karger journals aim to adhere to the COPE Code of Conduct and Best Practice Guidelines .
The presentation of manuscripts should follow the Uniform Requirements for Manuscripts Submitted to Biomedical Journals from the International Committee of Medical Journal Editors (ICMJE) . We recommend preparing the manuscript using the dedicated article template for the manuscript type.
Only papers written in English are considered. The articles should be comprehensible to a reader who is fluent in English and should be edited prior to submission to ensure that standard English grammar and usage are observed. Use of a professional language editing service prior to submission can help avoid delays with the review process.
Karger recommends the use of original images and materials whenever possible. If a submitted manuscript contains third-party copyright material(s), it is the authors’ sole responsibility to obtain permission from the relevant copyright holder for reusing the material(s), including any associated licensing fee. The copyright and usage information needs to be checked carefully to avoid copyright infringement. The author(s) is and will remain personally liable for any copyright infringements.
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Karger Publishers is a member of the Committee on Publication Ethics (COPE). Karger journals aim to adhere to the COPE Code of Conduct and Best Practice Guidelines . Our policies on reporting and investigation of suspected misconduct in manuscripts and articles and how we handle potential errors in published articles can be found on the Publication Ethics and Editorial Policies page. Concerns regarding a manuscript in review or a published article should be raised to the Research Integrity and Publication Ethics team at Publication Ethics .
All submitted manuscripts must contain a statements section after the main body of the text, but before the reference list. A summary of the required information is given below, for full details please refer to the article templates and visit the Publication Ethics and Editorial Policies page.
Acknowledgement (optional)
In the Acknowledgement section, authors may include individuals, who are not listed as authors, and organizations that have made substantive contributions to the research or the manuscript. An exception is where funding was provided, which should be included in Funding Sources.
Statement of Ethics
The Statement of Ethics must provide detail about the ethical approval process for the study reported in the manuscript, including the name and affiliation of the committee who approved the study and the decision reference number. For studies involving human participants, information must be provided about the consent provided to participate in the study. If information is included in the submission that may identify and individual or groups of individuals, specific consent to publish this information must be obtained and reported in the Statement of Ethics.
For complete information on our policies on Studies Involving Human Subjects, Identifiable Materials or Data or Studies Involving Animals, please see here .
Conflict of Interest Statement
Authors are required to disclose any relationship that could be perceived as a conflict of interest in the Conflict of Interest Statement. All forms of support and financial involvement which took place in the previous three years should be listed, regardless of their potential relevance to the paper. Nonfinancial relationships that may potentially influence the writing of the manuscript should also be declared. If there is no potential conflict of interest to report, please state this.
For complete information on our Conflict of Interest policy, please see here .
Funding Sources
Authors must give full details about the funding of any research relevant to their study, including sponsor names, written in full providing any associated grant numbers, and explanation of the roles of these funders in the study design, execution and analysis, and manuscript conception, planning, writing and decision to publish. If the sponsor or funder had no role in any of the above or if no funding was received for the study, please state this.
For complete information on our Funding Sources policy, please see here .
Author Contributions
In the Author Contribution statement, a short statement detailing the contributions of each person named as an author should be included. The CRediT taxonomy is a useful framework for preparing this section. Contributors to the submission who do not fulfil the ICMJE Criteria for Authorship should be credited, with their consent, in the Acknowledgement section.
For complete information on our Authorship and Contributorship policy, please see here .
Data Availability Statement
Authors are required to provide a Data Availability Statement that details whether data are publicly available and where the data supporting their study can be accessed. The journal’s data sharing policy strongly encourages authors to make all datasets on which the conclusions of the paper rely available to editors, reviewers and readers without unnecessary restriction wherever possible. In cases where research data are not publicly available on legal or ethical grounds, this should be clearly stated along with any conditions for accessing the data.
For complete information about our Data Sharing policy, please see here .
Further Conditions
Peer review.
Peer Review Policy
All Karger journals employ a rigorous peer-review process to confirm the validity and ensure scientific accuracy of published articles. Independent researchers with relevant expertise assess submitted manuscripts to help journal editors determine whether a manuscript should be published in their journal. All articles, except for Editorials and some Correspondence articles, are externally peer reviewed, typically by at least two individuals with expertise in the manuscript content area and/or research methods, before a final decision is made about acceptance for publication.
Peer Review Type and Process
Case Reports in Neurology uses a single-blind peer review system where reviewers know the names of the authors, but the authors do not know who reviewed their manuscript. For full details, including information about peer review policies and appeals process, please visit the Peer review – Karger Publishers page.
Article Preparation
The preferred word processing program for manuscripts is Microsoft Word. Page and line numbering should be activated, and the level of subheadings should be indicated clearly.
Footnotes should be avoided. When essential, they should be numbered consecutively and appear at the foot of the appropriate page.
Abbreviations (with the exception of those clearly well established in the field) should be explained when they are first used both in the abstract and in the main text.
Units of measurement should be expressed in SI units wherever possible.
Generic names of drugs (first letter: lowercase) should be used whenever possible. Registered trade names (first letter: uppercase) should be marked with the superscript registration symbol ® or ™ when they are first mentioned.
The manuscript text, tables and figures must be submitted in separate files. Figure legends should be included at the end of manuscript text, not in the figure file. Table headers should be included above or below the table in the table file.
For full technical specifications, including those regarding tables, figures, and illustrations, please refer to Karger’s Technical Instructions to Publish a Paper .
Manuscript Arrangement
The first page should contain a short and concise title plus a running head of no more than 80 characters. Abbreviations should be avoided.
Below the title, list all the authors’ names as outlined in the article sample, which can be downloaded under Article Types. Each listed author must have an affiliation, which comprises the department, university, or organization and its location, city, state/province (if applicable), and country.
Corresponding author information: Please supply the first and last name as well as an e-mail address at the bottom of the title page.
Keywords relevant to the article should be listed below the corresponding author information.
Please refer to the Article Types section of the Guidelines for Authors for information on the relevant article structure, including maximum word counts and downloadable samples.
In-Text Citation
References in the text should be identified sequentially using Arabic numerals [in square brackets].
Reference List
The reference list should include only those publications which are cited in the text, arranged numerically in the order in which they are cited. Please number the reference list as shown below (i.e., without using full stops, brackets, etc.). The authors’ surnames should be followed by their initials with no punctuation other than a comma to separate individual authors. A maximum of 6 authors should be listed (followed by “et al.” if there are more than 6 authors). Material submitted for publication but not yet accepted should be referred to as “unpublished data” and should not be included in the reference list. Other pre-published or related materials with a DOI, e.g. preprint manuscripts, datasets, and code, may be included. More information on good referencing practice, as well as further examples, can be found in National Library of Medicine Style Guide for Authors .
Articles published in journals: 1 Sawant KV, Xu R, Cox R, Hawkins H, Sbrana E, Kolli D, et al. Chemokine CXCL1-mediated neutrophil trafficking in the lung: role of CXCR2 activation. J Innate Immun. 2015;6(7):647–58. (Journal names should be abbreviated according to the Index Medicus.)
Articles published only with DOI number: 2 Chen C, Hu Z. ApoE polymorphisms and the risk of different subtypes of stroke in the Chinese population: a comprehensive meta-analysis. Cerebrovasc Dis. DOI: 10.1159/000442678.
Monographs: 3 Matthews DE, Farewell VT. Using and understanding medical statistics. 5th ed, revised. Basel: Karger; 2015.
Edited Books: 4 Cohen SR, Gardner TW. Diabetic retinopathy and diabetic macular edema. In: Nguyen QD, Rodrigues EB, Farah ME, Mieler WF, Do DV, editors. Retinal pharmacotherapeutics. Dev Ophthalmol. Basel: Karger; 2016. Vol. 55; p. 137–46.
Websites: 5 Karger Publishers [Internet]. Basel: Transforming Vesalius: The 16th-Century Scientific Revolution Brought to Life for the 21st Century [cited 2013 Feb 4]. Available from: https://www.vesaliusfabrica.com/en/new-fabrica.html .
Figures and Tables
The figure legend should be placed at the end of the article, after the reference list. The figure legend should not be part of the figure file. Tables require a heading above or below the table in the table file. For more details please download the relevant article template from the section “Article Types”.
Online Supplementary Material
Online Supplementary Material may be used to enhance a publication and increase its visibility on the Web. Supplementary files (directly relevant but not essential to the conclusions of the paper) will undergo editorial review and should be submitted in a separate file with the original manuscript and with all subsequent submissions. The Editor(s) reserve(s) the right to limit the scope and length of supplementary material. Supplementary material must meet production quality standards for publication without the need for any modification or editing. For ease of reader access, we strongly recommend that files be less than 10 MB. Authors wishing to associate larger amounts of supplementary material with their article should deposit their data in an appropriate public data repository. Figures must have legends and tables require headings. All files must be named clearly. Acceptable files and formats are Word or PDF files, Excel spreadsheets (if the data cannot be converted properly into a PDF file), and multimedia files (MPEG, AVI, or QuickTime formats). All supplementary material should be referred to in the main text. A DOI number will be assigned to supplementary material, and it will be hosted online at https://karger.figshare.com under a CC BY license .
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Karger Publishers offer a range of services to assist authors with the preparation of their manuscript, including discounts for language editing services offered by third parties.
More information is available on the Author Resources section of the Karger homepage.
When submitting a manuscript, authors can add their ORCID number to their Karger account to ensure that their paper is accredited to them correctly.
Cost of Publication
Page charges/article processing charges.
Karger has established Transformative Agreements with many consortia and institutions that include full or partial coverage of the Article Processing Charges (APCs) and/or the Author’s Choice Open Access publication fees. Authors affiliated with those institutions can publish Open Access in all Karger journals and comply with Open Access mandates without incurring any additional costs or with reduced APCs. Find out here whether your Open Access charges are covered by an agreement. Find more information on Open Access charges and potential funding options here .
Upon acceptance, manuscripts will be subject to an Article Processing Charge (APC) of CHF 1,010.00 / USD 1,120.00 / EUR 990.00. Please note that all fees are subject to change.
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After acceptance and sharing policies, copyediting and proofs.
Manuscripts accepted for publication by Karger Publishers will undergo basic proofreading to check for obvious spelling and grammar mistakes. If you would prefer a more in-depth language editing service to improve clarity and style, please consult a service provider prior to submission. Please note that the use of a language editing service before submission is not a requirement for publication in the journal and does not guarantee that the manuscript will be considered for peer review or accepted.
Karger Publishers’ house style is based on internationally recognized standard manuals, including The Chicago Manual of Style .
Proof Central
An email containing a link to access the proofs will be sent to the contact author. The authors should check the document and respond to any questions that have been raised during copyediting within 48 hours. A provisional PDF can be viewed for an impression of the final layout of the manuscript.
Corrections to the text and tables should be made directly in the template. Changes to figures are discouraged but can be indicated with comments. Final layout and typesetting take place at a later stage.
Alterations made to proofs, other than the correction of errors introduced during production, are subject to review and may require editorial approval which could delay the publication of your manuscript
Please note that the revised proofs are not sent to the authors prior to typesetting and online publication unless there are exceptional circumstances. The article layout will be created according to the Karger standard.
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Articles published in Case Reports in Neurology are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license, unless otherwise agreed with Karger Publishers. When sharing or reusing any article, attribution must be given to the original source, using the statement "The final, published version of this article is available at http://karger.com/?doi=[insert DOI number]" (e.g., http://karger.com/?doi=10.1159/000365070). Reuse for commercial purposes requires permission from the publisher.
More information is available on the Karger website .
The copyright of the article is retained by the authors. The authors grant S. Karger AG, Basel, an exclusive unlimited license to publish the article under a Creative Commons license and identify S. Karger AG as the original publisher. Submission of a manuscript for publication implies the authors’ consent to publication under the applicable Creative Commons license and the terms and conditions of the Publisher’s Licensing Agreement.
Please note that metadata – essentially, data tags about article information such as authors and keywords that helps make articles discoverable by, for example, search engines – is governed by a separate policy. Refer to the FAQ on our Open Access web pages for details.
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All articles are archived in Portico. Articles may also be archived in PubMed Central if the journal is indexed there. Karger permits authors of Open Access articles to post the Version of Record (VOR) of their articles in Open Access repositories or on other websites. Preprints may be shared without restriction. Re-posted Open Access articles must follow the terms of the relevant Creative Commons license.
To ensure citations are credited to the Version of Record, Karger encourages authors to link to the published article on karger.com and include the following statement: "The Version of Record of this article is available at http://karger.com/?doi=[insert DOI number](e.g. http://karger.com/?doi=10.1159/000365070)."
Manuscripts to be archived in PubMed Central due to NIH funding requirements will be submitted by Karger on the authors’ behalf, as outlined under Funding Organizations. Karger policies on Open Access, licensing and self-archiving can also be found at Sherpa Romeo .
Funding Organizations
NIH-Funded Research
The US National Institutes of Health (NIH) Public Access Policy mandates that the Author's Accepted Manuscript must be archived in its digital repository PubMed Central (PMC) within 12 months of the official publication date. As a service to authors, Karger Publishers submits the Version of Record of Open Access NIH-funded papers to PMC upon publication.
To facilitate compliance with Coalition S/Plan S Open Access mandates, Karger publishes Plan S-funded Open Access articles with a CC BY license. Some Coalition S funders, such as Wellcome Trust, Bill & Melinda Gates Foundation and FWF, designate PMC as the repository in which to archive articles. Where PMC is the designated repository, Karger will deposit the Version of Record on the author’s behalf with the CC BY license. Authors should refer to their funders’ policies for details. Authors should check their funders’ requirements about how to declare their funding and any associated mandates within their manuscript.
Karger publishes some journals under the Transformative Journals model, compliant with Plan S. Find more information about Transformative Journals on the Karger website .
Karger Publishers also complies with other funders’ requirements for submission to PMC. Authors should inform Karger about their grant providers during submission and include information on their grants in the Funding Sources section of their papers.
More information on funding sources can be found on the Karger website .
Cover Letter
In your cover letter, please describe the gap in knowledge that this manuscript addresses, and discuss the implications, significance and novelty of your research for the Editor. Furthermore, please emphasize the unique and important contributions that your manuscript makes to our understanding of the field. If your submission is part of a special issue of the journal, please refer to the specific name of the special issue in your cover letter and specify who invited the submission where appropriate.
Manuscript Submission
Manuscripts should be submitted online via the Case Reports in Neurology submission and peer review system by the manuscript’s corresponding author. The corresponding (submitting) author will automatically be the contact person for the manuscript for the peer review and production process. For fee payment and license signing, the contact author will be the first listed corresponding author.
The corresponding (submitting) author is solely responsible for managing all communication between the journal and all co-authors and acts on behalf of all listed authors. This ensures that all correspondence reaches a unique contact and thereby secures swift communication in particular throughout the submission, peer review and production process. Articles can be published with more than one corresponding author (usually limited to three), but only the submitting author can be accommodated during the submission, peer review and production process.
The corresponding (submitting) author’s specific responsibilities include:
Ensuring all the listed authors have approved the manuscript submission to the journal and agreed to all of the content including the author list, including the Submission Declaration
Handling the revision(s) and re-submission(s) of the manuscript until acceptance
After acceptance, manuscript proof reading and approving the final proof
Acting as the point of contact for queries about the published article. It is their responsibility to inform all co-authors of any matters arising in relation to the published article including questions relating to publication ethics, availability of data, materials, etc.
Where there are multiple corresponding authors, the first listed corresponding author’s specific responsibilities include:
Upon acceptance, ensuring that all listed authors agree to the license agreement
Arranging for payment of Page Charges/Article Processing Charges where required. The affiliation of the corresponding author will be used to determine eligibility for discounted or waived charges including discounted or waived APCs under read and publish/offsetting/OA agreements
Please note that the author names entered into the manuscript submission and peer review system should be identical to the information presented on the title page of the manuscript, including the sequence of authorship. The author names submitted should reflect the official publication names. It is the submitting (corresponding) author’s responsibility to ensure the accuracy of all content in the proof, including the names of co-authors, addresses and affiliations.
Before submission, please read the Submission Guidelines in full for specific requirements for manuscript preparation.
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Multiple metal exposures associate with higher amyotrophic lateral sclerosis risk and mortality independent of genetic risk and correlate to self-reported exposures: a case-control study
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http://orcid.org/0009-0009-7966-1322 Dae-Gyu Jang 1 , 2 ,
http://orcid.org/0000-0001-9894-5325 Stuart A Batterman 6 ,
http://orcid.org/0000-0002-9162-2694 Eva L Feldman 1 , 2 ,
http://orcid.org/0000-0001-8780-6637 Stephen A Goutman 1 , 2
1 Department of Neurology , University of Michigan , Ann Arbor , Michigan , USA
2 NeuroNetwork for Emerging Therapies , University of Michigan , Ann Arbor , Michigan , USA
3 Department of Epidemiology , University of Michigan , Ann Arbor , Michigan , USA
4 Department of Biostatistics , Corewell Health , Royal Oak , Michigan , USA
5 Department of Biostatistics , University of Michigan , Ann Arbor , Michigan , USA
6 Department of Environmental Health Sciences , University of Michigan , Ann Arbor , Michigan , USA
Correspondence to Dr Stephen A Goutman; sgoutman{at}med.umich.edu
Background The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources.
Methods Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass spectrometry. ORs and HRs for each metal were computed using risk and survival models. Environmental risk scores (ERS) were created to evaluate the association between exposure mixtures and ALS risk and survival and exposure source. ALS (ALS-PGS) and metal (metal-PGS) polygenic risk scores were constructed from an independent genome-wide association study and relevant literature-selected single-nucleotide polymorphisms.
Results Plasma and urine samples from 454 ALS and 294 control participants were analysed. Elevated levels of individual metals, including copper, selenium and zinc, significantly associated with ALS risk and survival. ERS representing metal mixtures strongly associated with ALS risk (plasma, OR=2.95, CI=2.38–3.62, p<0.001; urine, OR=3.10, CI=2.43–3.97, p<0.001) and poorer ALS survival (plasma, HR=1.37, CI=1.20–1.58, p<0.001; urine, HR=1.44, CI=1.23–1.67, p<0.001). Addition of the ALS-PGS or metal-PGS did not alter the significance of metals with ALS risk and survival. Occupations with high potential of metal exposure associated with elevated ERS. Additionally, occupational and non-occupational metal exposures were associated with measured plasma and urine metals.
Conclusion Metals in plasma and urine associated with increased ALS risk and reduced survival, independent of genetic risk, and correlated with occupational and non-occupational metal exposures. These data underscore the significance of metal exposure in ALS risk and progression.
EPIDEMIOLOGY
Data availability statement
Data are available upon reasonable request.
https://doi.org/10.1136/jnnp-2024-333978
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Contributors D-GJ, JFD, LZ, KMB, BM, SB, ELF and SAG conceived and designed the study. ST and SAG contributed to the acquisition of the data. D-GJ, JD and KMB performed the statistical analyses. D-GJ, EK and SAG interpreted the data, drafted the text and prepared the figures. All authors critically reviewed and approved the final version of the manuscript. SAG is the guarantor of the study.
Funding Funding was provided by the National Institute of Neurological Disorders and Stroke (NINDS) (R01NS127188); National Institute of Environmental Health Sciences (NIEHS) (K23ES027221, R01ES030049); Centers for Disease Control and Prevention (R01TS000344); ALS Association (20-IIA-532, 20-PP-661); NeuroNetwork for Emerging Therapies; Peter R. Clark Fund for ALS Research; Robert and Katherine Jacobs Environmental Health Initiative; Richard Stravitz Foundation; Coleman Therapeutic Discovery Fund; Scott L. Pranger ALS Clinic Fund; the Dr. Randall W. Whitcomb Fund for ALS Genetics; University of Michigan. Metals analysis was carried out at the Dartmouth Trace Element Core Facility, which is supported by Dartmouth Cancer Center with NCI Cancer Center Support Grant 5P30 CA023108.
Competing interests ELF: Listed as inventors on a patent, Issue number US10660895, held by University of Michigan titled 'Methods for Treating Amyotrophic Lateral Sclerosis' that targets immune pathways for use in ALS therapeutics. SAG: Listed as inventors on a patent, Issue number US10660895, held by University of Michigan titled 'Methods for Treating Amyotrophic Lateral Sclerosis' that targets immune pathways for use in ALS therapeutics. Scientific consulting for Evidera.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
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Per week, neurologists saw 36% of their patients via telehealth. Telehealth enabled neurologists to provide high-quality care for many services. Most used cases were for follow up care, improving access and medication management. And 75% or more of telehealth visits were with established patients.
The temperature was 36.4°C, the heart rate 120 beats per minute, the blood pressure 171/90 mm Hg, the respiratory rate 22 breaths per minute, and the oxygen saturation 95% while the patient was ...
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Case Reports in Neurology is a peer-reviewed, open-access journal that publishes original case studies covering the entire spectrum of neurology. In addition to single case studies, the journal accepts papers discussing case series to address the range of clinical practice.
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Abstract. Objective: To examine the influence of various factors on the risk of sudden unexpected death in epilepsy (SUDEP). Methods: The authors investigated 154 cases in which a postmortem examination was performed. Each case had four controls with epilepsy from the community, matched for age and geographic location.
Background The pathogenesis of amyotrophic lateral sclerosis (ALS) involves both genetic and environmental factors. This study investigates associations between metal measures in plasma and urine, ALS risk and survival and exposure sources. Methods Participants with and without ALS from Michigan provided plasma and urine samples for metal measurement via inductively coupled plasma mass ...
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