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MS Differential dx Health Page

May 14, 2015 - 0 comments

What Neurologists Must Consider
What Neurologists  MUST Consider when Looking for Possible MS: Differential Diagnosis

There is great  frustration when a person is ill with suspected MS but can’t begin  treatment because the neurologist won’t/can’t move forward with a positive diagnosis;  it is entirely too easy to blame the doctor for being noncommittal and sometimes rightly so.  But often it might be that the doctor is trying to make the symptoms and evidence fit, and it just doesn’t.

A differential diagnosis is a standard medical practice – doctors must always consider what else might be bothering a patient and not jump to the first possible answer without considering other possibilities.  The doctor must be reasonably sure that the treatment offered is appropriate.  

Retrospective studies (looking back on large groups of people who already have the diagnosis) consistently show that about 10% of people with the diagnosis of MS are misdiagnosed; that  is another great point for strong consideration of the differential diagnosis .

The doctor doesn't need to investigate or look for everything that has ever mimicked MS, but must be thorough in investigating all the things that could cause the patient's problems, given the clues and flags.   The doctor who is not thorough in considering all the options is skating on the thin malpractice ice.

With Multiple Sclerosis, the list of other possible diseases is extensive, and the differential diagnosis list contains a wide variety of diseases, from Systemic Lupus to Migraines, Sarcodoisis, to many variations of cancer.

It is common for patients to feel that time is being wasted while going through the diagnostic process and better communication would help this misunderstanding .  Some doctors  do NOT discuss the differential with patients - fearing (often rightly so) of raising huge anxiety at the mention of the other possibilities.  Some patients NEED to know what is being considered and should convey this to the doctor.  The downside to knowing the differentials being considered  is 1) increased anxiety, 2) time commitment, and 3) being drawn into discussions about "What if?"  eg: What will we do if this is cancer?"  and wasting time discussing things that are still unknown.

In general, it seems neurologists tend to  discuss less than more.  The doctors should realize that the less they communicate, the more the patient is driven to go elsewhere to get answers - often this results in symptom surfing.  Or this sends the patient looking for a different doctor - this is part of the "shopping" process where we should be looking for the doctor whose communication style fits the needs of the patient.

To look at ways that doctors can process information as presented by patients and their exams and move forward with a diagnosis, an international panel of experts worked through a differential diagnostic process for Multiple Sclerosis.  The entire text of their report, Differential diagnosis of suspected  multiple sclerosis: a consensus approach,  can be accessed for free at

This group of renowned experts from a variety of specialties independently evaluated clinical and diagnostic test criteria and developed an extensive list of 79 red flags that can be used by doctors to tell them how the clinical signs they are looking at may relate to the diagnosis of MS.   These flags come from MRI data as well as clinical observation and are in three categories: major, intermediate and minor flags.

The major flags were almost unanimously selected by the experts as being a symptom of something other than MS.  That is important.  The major flags point toward a different diagnosis.  Are they proof-positive that no MS is present?  No , but the odds are pretty strong that the person does not have MS based on these symptoms.

Intermediate flags mean that there was a lack of agreement among the experts and the symptoms could  possibly eliminate MS from the choices.  The Intermediate  Flags indicate that a very thorough investigation must be made because of  that flag.  The diagnosis might still be MS, but the exclusion must be thoroughly investigated .

Minor red flags are the lowest grouping of differential symptoms.  The minor flags indicate that another disease may be causing the symptoms and should be considered,  but it is also possible that the symptom is caused by MS.   These are the symptoms that are least likely to cause a different diagnosis than MS.

The other significant part of this work was they developed  a grouping of strategies for doctors to consult when working up a diagnosis.  There are a number of Idiopathic Inflammatory Demyelinating Diseases  (IIDD) that could suggest MS but are really something else.    They tackled the tough process of labeling NMO and CIS as well.    The details of these, along with several  easy to understand flowcharts are also in this paper, and worth spending time to review.

Table 1 in the paper gives examples of alternative diagnosis for each of the red flag items.  The following list of flags and alterative diagnosis (in parenthesis)  is given as a partial example; the entire list and more details can be found within the text of the paper.


Bone lesions  (Histiocytosis)

Lung Involvement (Sarcodoisis)

Peripheral neuropathy (B12 deficiency, Lyme disease)

Cerebral venous sinus thrombosis (Vasculitis, Chronic meningitis)

Cardiac Disease  (cerebral infarcts. Brain abscesses)

Calcifications on CT scans (Mitochondrial disorders)

Lacunar infarts (Hyperintensive ischemic disease)

Diabetes Insipidus (Sarcoidosis, neuromyelitis optica)

Persistent GD-enhancement and continued enlargement of lesions (Lymphoma, glioma, vasculitis)

Hypothalamic disturbance (Sarcoidosis, neuromyelitis optica)

Simultaneous enhancement of all lesions ((Vaculitis, lymphoma)

Rash (Lupus, Lyme disease, T-cell lymphoma)

Headache (Venous sinus thrombosis, vasculitis, Lupus, meningitis)

Persistent monofocal  manifestations  (structural lesion, such as Chiari malformation)

Large and infiltrating brain stem lesions (pontine glioma)

INTERMEDIATE RED FLAG EXAMPLES  (strong evidence not MS but can’t be ruled out )

Punctiform parenchymal enhancement (Sarcoidosis, vasculitis)

Atrophy of the brainstem (Behcets disease, Alexander’s disease)

Loss of hearing (Susac’s syndrome, glioma)

Symmetrically distributed lesions (Leukodystrophy))

Complete ring enhancement  (Brain abscess, metastatic cancer)

Progressive ataxia alone (Multisystemm atrophy, cerebellar syndrome(

Central brainstem lesions (Hypoxicischim conditions, infarct)

Seizure (Whipple’s disease, vasculitis)

Dilation of the Virchow-Robin spaces (Primary CNS angitis)

Gradually progressive course from onset  (B12 deficiency)

MINOR RED FLAGS (MS must be considered as well as other diseases)

No enhancement (PML, Ischemic lesions)

No optic nerve lesions (metastatic carcinoma, toxoplasmosis)

Onset before age 20 (Mitochondrial encephalomyopathy, leukodystrophy)

Onset after age 50 (Cerebral infarction, lymphoma)

Marked asymmetry of white matter lesions (Gioblastoma, lymphoma, cerebral infarction)

No spinal cord lesions (Multiple infarcts, vasculitis, PML)

Large lesions (Gioblastoma, lymphoma, PML)

The patient perspective often is diagnosing neurological disorders such as MS should be a simple process; this cited work,  Differential diagnosis of suspected  multiple sclerosis: a consensus approach,  gives a different view of how complex the path to an Multiple Sclerosis diagnosis can be.

The bottom line to all this is if you are undiagnosed , the frustration of not having answers is understandable, but the neurologist is not necessarily to blame.  The doctors must proceed with caution and make sure that the diagnosis is accurate.   If your doctor is uncommunicative as to what the process is for your particular case, you may need to ask the questions about the differentials or move on to another doctor.

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Tags: Multiple Sclerosis, Neurology, possible ms, differential diagnosis for MS
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