Conversion disorder

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Conversion disorder
ICD-10 F44.
ICD-9 300.11
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Synonyms and Keywords: Functional neurological symptom disorder; functional neurological deficit; psychogenic movement disorders

Overview

Conversion Disorder is a DSM-IV diagnosis which describes neurological symptoms such as extreme weakness, paralysis, sensory disturbance, seizure and/or attacks that may resemble a known organic disease such as epilepsy or dystonia, but which cannot be currently attributed to neurological disease.

Definition

The definition of conversion disorder was historically associated with psychodynamic concepts, particularly in earlier versions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The most current definition is found in the 4th edition of the DSM (DSM-IV) and is as follows:

  • One or more symptoms or deficits are present that affect voluntary motor or sensory function suggestive of a neurologic or other general medical condition.
  • Psychological factors are judged, in the clinician's belief, to be associated with the symptom or deficit because conflicts or other stressors precede the initiation or exacerbation of the symptom or deficit. A diagnosis where the stressor precedes the onset of symptoms by up to 15 years is not unusual.
  • The symptom or deficit, after appropriate investigation, cannot be explained fully by a general medical condition, the direct effects of a substance, or as a culturally sanctioned behavior or experience.
  • The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.

It should be noted that this definition is not universally accepted by psychiatrists in the field. Some prefer to diagnose the disease according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) criteria, under which it is considered a disease of dissociation. Wessely school psychiatrists find the DSM completely irrelevant:

The suggested distinctions that appear to have some empirical and practical validation would be a diagnosis that continues to insist that either symptoms and/or loss of function be inexplicable in conventional biomedical terms and then distinguish between symptoms and loss of function, and between acute and chronic onset of either[1].

So that diagnosis is based on physical symptoms that the physician is able to explain based on their knowledge of disease and the "signs" of hysteria a patient may demonstrate. These signs are frequently inaccurate:

In an attempt to validate recent assertions that the strongest indicators of hysteria are the "positive" findings in the neurological examination, seven of the most accepted features (history of hypochondriasis, secondary gain, la belle indifference, nonanatomical sensory loss, split of midline by pain or vibratory stimulation, changing boundaries of hypalgesia, giveaway weakness) were sought in 30 consecutive neurology service admissions with acute structural nervous system damage. All subjects showed at least one of these findings; most presented three or four. The presence of these "positive" findings of hysteria in patients with acute structural brain disease invalidates their use as pathognomonic evidence of hysteria. A second, retrospective study on the misdiagnosis of hysteria demonstrated that women, homosexual men, the psychiatrically ill, and patients presenting plausible psychogenic explanations for their illness are most liable to be misdiagnosed. Certain disorders, particularly movement disorders and paralysis, are most often mislabeled as hysteria. A diagnosis of hysteria must be made with great caution as it so often proves incorrect.[2]

Terminology

The terminology surrounding conversion disorder is complex. Symptoms may also be described as "functional", "non-organic", "hysterical", or "psychogenic", according to preference or different Etiology|aetiological points of view. Critics claim that the diagnosis is essentially a belief system based upon the Judeo-Christian|Judaeo-Christian tradition that influenced much of Freud's thinking (see why Freud was Wrong, Webster)

Another term that has been suggested for conversion disorder is "Functional Neurological Deficit", which research has shown to be a more acceptable term in doctor-patient relationships

Historical Perspective

Historically, women presenting with symptoms lacking an obvious underlying physical cause were diagnosed as having "female hysteria"; a term which could refer to a wide spectrum of symptoms ranging from fainting to anxiety. The concept of "hysteria" (from the Greek hysterikos) dates back over 2,000 years and was thought to relate to abnormal motions of the uterus. From the 17th century onwards, Thomas Willis, Robert Whytt and others increasingly realised the problem was in fact located in the brain.

In the 19th century, physicians such as Silas Weir Mitchell in the US and Paul Briquet and Jean-Martin Charcot in France developed ideas about patients sharing unexplained neurological symptoms. Charcot specialised in treating patients who were suffering from a variety of unexplained physical symptoms including paralysis, contractures (muscles which contract and cannot be relaxed) and seizures. Some of these patients sporadically and compulsively adopted a bizarre posture (christened arc-de-cercle) in which they arched their body backwards until they were supported only by their head and their heels.

"Charcot eventually came to the conclusion that many of his patients were suffering from a form of hysteria which had been induced by their emotional response to a traumatic accident in their past – such as a fall from a scaffold or a railway crash. They suffered, in his view, not from the physical effects of the accident, but from the idea they had formed of it... However many of the most basic diagnostic techniques which are taken for granted by modern physicians had still to be discovered. The lumbar puncture, which is the only way in which Breuer could have tested his momentary hunch that Anna O. was suffering from meningitis, was not developed until 1891, and was not in general use until the early part of the twentieth century. X-rays, which would eventually become one of the most useful of all diagnostic aids, were discovered only in 1895 – the same year in which Studies on Hysteria was published. The electroencephalogram, which would revolutionise neurology and psychiatry and lead to the final definition of temporal lobe epilepsy, was not invented until 1929, and was not in general use until the 1940s. Many other basic techniques of neurological investigation would not be developed until even later. The computed tomography scan, for example, which uses X-ray transmission readings to generate an image of the brain and which can display some lesions, tumours and other signs of pathology directly, began to be generally used only in the late 1970s. Not only were these diagnostic techniques unavailable to Breuer, Freud and their contemporaries, but neurology and psychiatry were relatively young and under-organised branches of medicine whose stores of knowledge were only just beginning to be built up." (Webster) [3]

It is also now recognised that many of Charcot's demonstrations of hysteria were faked (Thomas Szasz|Szasz, the Myth of Mental Illness). As many neurologists remain ignorant of Charcot's methodology at the Salpêtrière in the diagnosis of hysteria, he is often held up as a champion of neuropsychiatry (Stone et al). It is doubtless though that as neurology continues to emerge from diagnostic darkness further techniques are likely to be developed and previously unvisualised abnormalities and conditions recognised.Template:Fix/category[citation needed]

The term "Conversion disorder" is a legacy of Freud and the psychotherapy movement. He viewed these apparently neurological symptoms as a result of the conversion of intrapsychic distress in to physical symptoms. It is worth bearing in mind that much of Freud's work is now viewed with Freud#Critical reactions|scepticism, and it may be that patients Freud thought were hysterical may actually have suffered from organic illness, such as "Anna O."[4]

In the 1960s the London Psychiatrist Eliot Slater recognised that finding a life event just before the onset of a symptom was an entirely unreliable way of diagnosing conversion disorder.Template:Fix/category[citation needed]

“Unfortunately we have to recognise that trouble, discord, anxiety and frustration are so prevalent at all stages of life that their mere occurrence near to the time of onset of an illness does not mean very much.” — Eliot Slater

He also suggested that conversion disorder was largely a 'delusion and a snare' since many of the people said to have it would eventually go on to develop a neurological disease that in hindsight could explain their original symptoms. This echoed the earlier sentiments of Steyerthal:

"Within a few years the concept of hysteria will belong to history ... there is no such disease and there never has been. What Charcot called hysteria is a tissue woven of a thousand threads, a cohort of the most varied diseases, with nothing in common but the so-called stigmata, which in fact may accompany any disease." — Armin Steyerthal (1908)[5]

Studies since 1970 have shown that misdiagnosis still occurs but at a rate of around 5% which is the same as for other neurological and psychiatric symptoms[6]. However Canadian studies[7] find a misdiagnosis rate in 80% of patients labelled with CFS/functional symptoms. In the United Kingdom it would appear that the diagnosis rate is a social phenomenon produced by the modus operandi of health care systemsTemplate:Fix/category[citation needed]. Most patients only receive investigations at the onset of illness Template:Fix/category[citation needed] and many illnesses, such as MS, are hard to diagnose initially. Patients also tend to produce functional symptoms in response to the disbelief and prompting of a neurologist as Slater also recognisedTemplate:Fix/category[citation needed]. Inconsistency could thus be seen as merely an expression of self-consciousness and desperation in the light of distressing symptomsTemplate:Fix/category[citation needed]. It is interesting in this light to note however that 20% of MS patients are re-classified as having functional symptoms and there is a high co-morbidity of functional symptoms alongside recognised organic brain disease. This was first recognised by the neurologist Arthur Hurst in his work on soldiers suffering from functional symptoms following organic illness.Template:Fix/category[citation needed]

Historically, conversion disorder was thought to manifest itself in many different ways. Conversion disorders were thought to be triggered by acute psychosocial stress that the individual could not process psychologically. This overwhelming distress was thought to cause the brain to unconsciously disable or impair a bodily function which would relieve or prevent the patient from experiencing this stressor again. This is in stark contrast to the modern understanding that patients remain distressed by their symptoms in the long term[8] and generally any hypothesised stressor is removed temporally and symbolically from the onset of symptoms. Therefore, the psychosocial stress cannot be seen to be "converted" into a physical symptom that relieve suffering, when in actual fact they increase it.

More recently, research is attempting to examine the complex nature of these symptoms and the absurdity of a dualist approach which attempts to suggest that symptoms are either all organic or all psychiatric. Functional neuroimaging has shown intriguing findings with respect to the neural correlates of these symptoms, the best example given by Vuilleumier[9]. Vuilleimier's statement when interviewed that this "supports Freud's hypothesis" is considered to be deeply inaccurate by Freudian scholars, as Vuilleimier's findings of abnormal cerebral perfusion do not fit anatomically with the autonomous unconscious of classical Freudian thought.

Causes

Studies report that 64% of patients with conversion disorder show evidence of an organic brain disorder, compared with 5% of control subjects. Only 7% of patients with medically unexplained symptoms eventually receive a diagnosis. There is a high mortality rate amongst this 7%.

Some bacterial and viral pathogens can also mirror conversion symptoms and non-pyramidal weakness as they alter brain chemistry and function rather than gross structure (forthcoming publication). Charcot hypothesised that functional symptoms were caused by dynamic lesions—abnormal cerebral perfusion. With Hughes syndrome, B12 deficiency and other blood disorders causing symptoms that mimic conversion disorder it would Appear that Charcot's lesions are likely to prove organic in origin. ME/CFS also show abnormalities in cerebral perfusion markedly different from clinical depression.

Differential Diagnosis

Epidemiology and Demographics

Prevalence

In the US

The precise prevalence of conversion disorder is unknown[10]. Predisposing factors, according to the DSM-IV, include prior physical disorders, close contact to people with real physical symptoms, and extreme psychosocial stress. In the United Kingdom however 40% of neurological referrals are deemed to be suffering from conversion disorder[11].

Incidence has been reported to be 15-22 cases per 100,000 people. In patients with chronic pain, incidence was 0.22%. Conversion reaction may occur more often in rural settings, where patients may be naive about medical and psychological issues. In one study, high rates were seen in Appalachian males. The disorder is observed more commonly in lower socioeconomic groups and may be more common in military personnel exposed to combat situations.

Cultural factors may play a significant role. Symptoms that might be considered a conversion disorder in the US may be a normal expression of anxiety in other cultures.

One study reports that conversion disorder accounts for 1.2-11.5% of psychiatric consultations for hospitalized medical and surgical patients.

Internationally

At the National Hospital in London, the diagnosis was made in 1% of inpatients. Iceland's diagnosis of conversion disorder is reported to be 0.00015% [12]. Eastern Turkey has a higher rate than the more affluent western regions where medical facilities are more sophisticated.[13]. In Eastern Libya the incidence is 8.3%. In Saudi Arabia the rate is 5.1% with a 2:1 ratio of women to men. Egypt in the 1960s had a diagnosis rate of 11.2%.[14]

Incidence disparity due to sex

Sex ratio is not known although it has been estimated that women patients outnumber men by 6:1. Many authors have related the development of conversion disorder in women with sexual maladjustment. Other authors disagree, stating that men are as likely to experience conversion symptoms as women. Men seem to be especially prone if they have suffered an industrial accident or have served in the military. In a study at the University of Iowa conducted from 1984-1986, patients diagnosed with conversion disorder were in large part men, especially those with a history of military combat.[15]

Risk Factors

Natural History, Complications and Prognosis

Prognosis

Good prognostic factors include:[10]

  • Short duration of symptoms
  • Acceptance of the diagnosis

Poor prognostic factors include:[10]

  • Maladaptive personality traits
  • Comorbid physical disease
  • Receipt of disability benefits

Diagnosis

Conversion disorder can present with any motor or sensory symptom in the body including

  • Weakness / Paralysis of a limb or the entire body hysterical paralysis or motor conversion disorders
  • Impaired hearing or vision
  • Loss / Disturbance of sensation
  • Impairment or loss of speech; hysterical aphonia
  • Psychogenic non-epileptic seizures
  • Fixed Dystonia unlike normal dystonia
  • Tremor, Myoclonus or other movement disorders
  • Astasia-abasia or Gait Problems
  • glove anesthesia (even though this is now recognised as a vascular disorder related to certain forms of dermatitis[16])
  • hysterical pregnancy (even though though this is common in other mammals to ensure enough milk for the group's offspring)[17]

Diagnosis depends not on the absence of findings of neurological disease but on the subjective discerning of positive evidence of conversion symptoms.

Historically, a symptom of conversion disorder thought to be diagnostic was La belle indifférence, described in DSM-IV as "a relative lack of concern about the nature or implications of the symptoms". However, a recent study found no evidence that patients with "functional" symptoms are any more likely to exhibit this than patients with a confirmed "organic" disease. [18] Another feature thought to be diagnostic was that symptoms would tend to be more severe on the non-dominant (usually left) side; there were a variety of theories such as the relative involvement of cerebral hemispheres in emotional processing, or more simply just that it was "easier" to live with a functional deficit on the non-dominant side. However a literature review of 121 studies established that this was not true, with publication bias the most likely culprit for the erroneous belief. [19]

Patients often deny emotional difficulty. Traditionally associated with conversion disorder, la belle indifférence, histrionic personality, and secondary gain are clinical features that appear to have no diagnostic significance. Although presence of these features supports the diagnosis, they have no diagnostic validity because the diagnosis of conversion disorder ultimately depends upon clinical findings that clearly demonstrate that the patient's symptomatology is not caused by organic disease. [20]

One study reported 5 patients with hysterical conversion reactions after injury or infarction to the left cerebral hemisphere.[21]

Conversion symptoms are remarkably consistent between patients, just as Parkinson's disease is consistent between patients. There may be positive evidence of patterns of weakness (for example, Hoover's sign or a non-pyramidal pattern of weakness) or a typical gait problem (for example a 'dragging monoplegic gait). For psychogenic non-epileptic seizures a range of features of the attacks must be taken in to consideration and the diagnosis may need confirmation with videotelemetry.

Diagnosis is not easy and should preferably only be made by a neurologist with experience of the condition. The Nightingale Foundation has however found that 80% of patients with functional symptoms are misdiagnosed [22] with diagnostic procedures by most physicians of poor quality and tests been far from exhaustive. The common procedure of neurologists relying on the reports of radiologists rather than viewing MRI scans themselves is seen as deeply flawed.

Patients with conversion symptoms will typically have multiple other symptoms which may include fatigue, sleep disturbance, memory and concentration difficulties, pain (neck, back, muscles), bowel and bladder sensitivity.

Diagnostic Criteria

DSM-V Diagnostic Criteria for Conversion Disorder[10]

  • A.One or more symptoms of altered voluntary motor or sensory function.

AND

  • B.Clinical findings provide evidence of incompatibility between the symptom and recognized neurological or medical conditions.

AND

  • C.The symptom or deficit is not better explained by another medical or mental disorder.

AND

  • D.The symptom or deficit causes clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.

Specify symptom type:

  • With weakness or paralysis with abnormal movement (e.g., tremor, dystonic movement, myoclonus, gait disorder)
  • With swallowing symptoms
  • With speech symptom (e.g., dysphonia, slurred speech)
  • With anesthesia or sensory loss
  • With special sensory symptom (e.g., visual, olfactory, or hearing disturbance)
  • With mixed symptoms

Specify if:

  • Acute episode; Symptoms present for less than 6 months.
  • Persistent: Symptoms occurring for 6 months or more.

Specify if:

  • With psychological stressor (specify stressor)
  • Without psychological stressor

Differential diagnosis

Conversion disorder must be differentiated from other causes of headache,seizures and loss of consciousness.

Diseases Symptoms Physical Examination Past medical history Diagnostic tests Other Findings
Headache LOC Motor weakness Abnormal sensory Motor Deficit Sensory deficit Speech difficulty Gait abnormality Cranial nerves CT /MRI CSF Findings Gold standard test
Meningitis + - - - - + + - - History of fever and malaise - Leukocytes,

Protein

↓ Glucose

CSF analysis[23] Fever, neck

rigidity

Encephalitis + + +/- +/- - - + +/- + History of fever and malaise + Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Brain tumor[24] + - - - + + + - + Weight loss, fatigue + Cancer cells[25] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + - Hypertension + - CT scan without contrast[26][27] Neck stiffness
Subdural hemorrhage + + + + + - - - + Trauma, fall + Xanthochromia[28] CT scan without contrast[26][27] Confusion, dizziness, nausea, vomiting
Neurosyphilis[29][30] + - + + + + - + - STIs + Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[31]

Blindness, confusion, depression,

Abnormal gait

Complex or atypical migraine + - + + - - + - - Family history of migraine - - Clinical assesment Presence of aura, nausea, vomiting
Hypertensive encephalopathy + + - - - - + + - Hypertension + - Clinical assesment Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy - + - - - + + + + History of alcohal abuse - - Clinical assesment and lab findings Ophthalmoplegia, confusion
CNS abscess + + - - + + + - - History of drug abuse, endocarditis, immunosupression + leukocytes, glucose and protien MRI is more sensitive and specific High grade fever, fatigue,nausea, vomiting
Drug toxicity - + - + + + - + - - - - Drug screen test Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder + + + + + + + + History of emotional stress - - Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia) - + + + + + - - + - - Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia Depends on the cause Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation - - + + - + + + + History of relapses and remissions + CSF IgG levels

(monoclonal bands)

Clinical assesment and MRI [32] Blurry vision, urinary incontinence, fatigue
Seizure + + - - + + - - + Previous history of seizures - Mass lesion Clinical assesment and EEG [33] Confusion, apathy, irritability,


Influence of age and life experience

Conversion disorder may present at any age but is rare in children younger than 10 years or in persons older than 35 years. Some studies have reported another peak for patients aged 50-60 years.

In a University of Iowa study of 32 patients with conversion disorder, however, the mean age was 41 years with a range of 23-58 years.

In pediatric patients, incidence of conversion is increased after physical or sexual abuse. Incidence also increases in those children whose parents are either seriously ill or have chronic pain[34]. Parents whose children develop illness that cannot be medically explained are at risk of being charged with Munchausen syndrome by proxy. [35]

Conversion disorder versus malingering

Often patients' reaction to the diagnosis of conversion disorder is to be offended that the doctor thinks they are crazy or making their symptoms up. Many doctors still regard these symptoms as 'not genuine' and not deserving of attention. However, many doctors do regard them as genuine but struggle to know how to communicate with patients.

Patients suffering from conversion disorder often have very little to gain from their disorder, while malingerers by necessity gain through avoidance of work, financial compensation, or other reward.

If patients with conversion symptoms were malingering there would be a number of problems from clinical practice to sort out:

  • Evidence from long term studies showing that symptoms persist at follow up many years later
  • Patients with conversion symptoms generally desire tests while malingerers do not
  • There is remarkable consistency between unrelated patients with this disorder

Treatment

Treatment may include the following:

  1. Explanation. This must be clear and coherent. It must emphasise the genuineness of the condition, that it is common, potentially reversible and does not mean that the sufferer is a 'psycho'. Taking an aetiologically neutral stance by describing the symptoms as functional may be helpful but further studies are required. Ideally the patient should be followed up neurologically for a while to ensure that the diagnosis has been understood.
  2. Physiotherapy where appropriate;
  3. Treatment of comorbid depression or anxiety if present.

There is little evidence-based treatment of conversion disorder[36]. Other treatments such as cognitive behavioral therapy, hypnosis, EMDR, and psychodynamic psychotherapy need further trials. It should also be noted that psychoanalytic treatments, on which CBT is based, were singularly ineffective with Freud and Breuer's patients.

References

  1. Wessely, in Contemporary Approaches to the Study of Hysteria, Ed. Halligan, Bass and Marshall OUP, 2001
  2. Gould R, Miller BL, Goldberg MA, Benson DF (1986) “The validity of hysterical signs and symptoms.”Journal of Nervous and Mental Disease, 174, 593–597. PMID: 3760849
  3. Webster, Why Freud Was Wrong
  4. Alison Orr-Andrewes, "The case of Anna O: A Neuropsychiatric perspective", Journal of the Psychoanalytic Association 1987, vol 35 p.399.
  5. Armin Steyerthal, Was ist Hysterie? Eine Nosologische Betrachtung, Halle: Carl Marhold Verlag, 1908.
  6. Stone, et al, BMJ 2005
  7. Hyde, The complexity of diagnosis
  8. Stone, et al, JR Soc Med 2005; 98:547-548
  9. Vuilleumier, et al, Brain, Vol. 124, No. 6, pp. 1077-1090, June 2001
  10. 10.0 10.1 10.2 10.3 10.4 10.5 Diagnostic and statistical manual of mental disorders : DSM-5. Washington, D.C: American Psychiatric Association. 2013. ISBN 0890425558. 
  11. Stone, Carson & "Wessely School" psychiatrists
  12. Powsner, Dufel, ibid.
  13. M. Kuloglu, M. Atmaca1, E. Tezcan1, O. Gecici1, S. Bulut, "Sociodemographic and clinical characteristics of patients with conversion disorder in Eastern Turkey", Social Psychiatry and Psychiatric Epidemiology, 38(2003) pp 89-93.
  14. Tariq Ali Al-Habeeb, Khalid Al-Zaid, Fath El Aleem Abdul Rahim, Eiad A. Al-Faris, "Hysteria: A Clinical and Sociodemographic Profile of 40 Patients Admitted to a Teaching Hospital, 1985-1995", Ann Saudi Med 1997;17(1) pp.35-38.
  15. Powsner, Dufel, ibid.
  16. Byron Hyde MD
  17. Danusa Guedesa, Robert John Young, "A Case of Pseudo-Pregnancy in Captive Brown Howler Monkeys (Alouatta guariba)", Folia Primatologia, 75(2004) pp 335-338.
  18. Stone J, Smyth R, Carson A, Warlow C, Sharpe M., "La belle indifference in conversion symptoms and hysteria: systematic review." Br J Psychiatry. 2006 Mar;188 pp.204-9.
  19. Stone J, Sharpe M, Carson A, Lewis SC, Thomas B, Goldbeck R, Warlow CP. "Are functional motor and sensory symptoms really more frequent on the left? A systematic review." J Neurol Neurosurg Psychiatry. 2002 Nov;73(5) pp.578-81.
  20. Seth Powsner, Susan Dufal, "Conversion disorder", e-medicine from WebMD
  21. ibid.
  22. Byron Hyde, The Complexities of Diagnosis, Handbook of ME
  23. Carbonnelle E (2009). "[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent].". Med Mal Infect. 39 (7-8): 581–605. PMID 19398286. doi:10.1016/j.medmal.2009.02.017. 
  24. Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke.". J Neurooncol. 44 (1): 47–52. PMID 10582668. 
  25. Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions.". Fluids Barriers CNS. 8 (1): 14. PMC 3059292Freely accessible. PMID 21371327. doi:10.1186/2045-8118-8-14. 
  26. 26.0 26.1 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke.". West J Emerg Med. 12 (1): 67–76. PMC 3088377Freely accessible. PMID 21694755. 
  27. 27.0 27.1 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease.". J Am Coll Radiol. 8 (8): 532–8. PMID 21807345. doi:10.1016/j.jacr.2011.05.010. 
  28. Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction.". Stroke. 6 (6): 638–41. PMID 1198628. 
  29. Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients.". J Neurol Sci. 317 (1-2): 35–9. PMID 22482824. doi:10.1016/j.jns.2012.03.003. 
  30. Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. PMID 24365430. doi:10.1016/B978-0-7020-4088-7.00098-5. 
  31. Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. PMC 3746559Freely accessible. PMID 22421697. doi:10.1097/OLQ.0b013e31824ee574. 
  32. Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.". Arch Neurol. 51 (1): 61–6. PMID 8274111. 
  33. Manford M (2001). "Assessment and investigation of possible epileptic seizures.". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557Freely accessible. PMID 11385043. 
  34. Powsner, Dufel, ibid.
  35. Virginia T. Sherr, "Munchausen's syndrome by proxy and Lyme disease: medical misogyny or diagnostic mystery?", Medical Hypotheses, 2005;65(5) pp.440-447
  36. Ruddy and House, Cochrane Collaboration
nl:Conversiestoornis



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