Idiopathic inflammatory demyelinating diseases

Idiopathic inflammatory demyelinating diseases (IIDDs), sometimes known as borderline forms of multiple sclerosis,^[1] is a collection of multiple sclerosis variants, sometimes considered different diseases,^[2][3] but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.^[4][5]

Contents 1 Diseases included in this category 2 Clinical courses inside standard MS 2.1 Progressive variants 2.2 Subclinical, preclinical, CIS and CDMS 2.3 Aggressive multiple sclerosis 2.4 Pediatric and pubertal MS 3 Controversy for the definition 3.1 Clinical vs. pathological definitions 3.2 Current definitions 4 See also 5 References

Diseases included in this category

The list of these diseases depends of the author, but usually are included:

• Standard multiple sclerosis, the most known and extended variant.
• Optic-spinal MS, or Opticospinal, variant which often include visual symptoms and have a more severe course than typical MS. Though multiple scars (scleroses) are present in CNS, and sometimes Poser criteria classifies it as clinically definite multiple sclerosis,^[6] currently is considered outside the scope of Multiple Sclerosis and inside the scope of Devic's disease,^[7] though is not sure if this applies to all cases.^[8]
• Devic's disease, currently considered a separate disease
• Acute disseminated encephalomyelitis or ADEM, a closely related disorder in which a known virus or vaccine triggers autoimmunity against myelin.
• Acute hemorrhagic leukoencephalitis, possibly a variant of Acute disseminated encephalomyelitis
• Balo concentric sclerosis, an unusual presentation of plaques forming concentrenic circles, which can sometimes get better spontaneously.
• Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural demyelinating lesion; and is more common in children.^[9][10]
• Marburg multiple sclerosis, an aggressive form, also known as malignant, fulminant or acute MS.

• Tumefactive Multiple sclerosis: lesions whose size is more than 2 cm, with mass effect, oedema and/or ring enhancement^[11][12]

• Venous multiple sclerosis: A relationship has been proposed between MS and Chronic cerebrospinal venous insufficiency. The hypothetical MS variant produced by CCSVI is called Venous Multiple Sclerosis. If this hypothesis is confirmed, this variant would account for most of MS cases.
• Leukodystrophy (which see) and its sub-conditions:
  • Adrenoleukodystrophy
  • Adrenomyeloneuropathy

Some others include in the list also other conditions associated with the presence of the scleroses^[13]

• Optic neuritis (monophasic and recurrent)
• Transverse myelitis (monophasic and recurrent)

As MS is an active field for research, the list is not closed or definitive. For example, some diseases like Susac's syndrome (MS has an important vascular component^[14]), Myalgic encephalomyelitis (aka Chronic fatigue syndrome)^[15] or autoimmune variants of peripheral neuropathies like Guillain-Barré syndrome or Progressive inflammatory neuropathy could be included assuming the autoimmune model.

Clinical courses inside standard MS

Also inside standard MS different clinical courses can be separated.

Progressive variants

Some authors also think that primary progressive multiple sclerosis should be considered a different entity from standard MS.^[16][17] Others maintain the opposite.^[18] In any case, the lesions in PPMS can be diffused instead of the normal focal ones.^[19] Finally, also a dual classification of these diseases has been proposed, according to the shape of edges of the scars, in MS-like and ADEM-like^[20]

Subclinical, preclinical, CIS and CDMS

The first manifestation of MS is the so called Clinically isolated syndrome, or CIS, which is the first isolated attack. The current diagnosis criteria for MS does not allow doctors to give an MS diagnosis until a second attack takes place. Therefore the concept of "clinical MS", for a MS that can be diagnosed has been developed. Until MS diagnosis has been established, nobody can tell whether the disease dealing with is MS.

Cases of MS before the CIS are sometimes found during other neurological inspections and are referred to as subclinical MS.^[21] Preclinical MS refers to cases after the CIS but before the confirming second attack.^[22] After the second confirming attack the situation is referred to as CDMS (clinically defined multiple sclerosis).^[23]

Aggressive multiple sclerosis

Relapsing-Remitting MS is considered aggressive when the frequency of exacerbations is not less than 3 during 2 years. Special treatment is often considered for this subtype.^[24]

Pediatric and pubertal MS

MS cases are rare before puberty, but they can happen. Whether they constitute a separate disease is still an open subject. Anyway, even this pubertal MS could be more than one disease, because early-onset and late-onset have different demyelination patterns^[25]

Controversy for the definition

Clinical vs. pathological definitions

Probably the most implicitly used definition can be found into the McDonald criteria proposal, which is the currently considered as the gold standard for MS diagnosis. These authors state that "MS is a clinical entity and therefore should be diagnosized with clinical and paraclinical criteria"^[26] . Currently the McDonald criteria are considered a clinical definition of MS.

Some other authors consider MS as a pathological entity instead, and propose a pathological definition. According to Hans Lassmann, the pathological definition should be preferred because clinical definitions have problems with differential diagnosis.^[27] Of course, using a pathological definition would not prevent performing clinical diagnosis, but would require to calibrate any diagnosis criteria against it.

McDonald et al. do not agree with this, and they remark the clinical character of MS. They state that "Whereas it might be said that the only proved diagnosis of MS can be made upon autopsy, or occasionally upon biopsy, where lesions typical of MS can be directly detected through standard histopathological techniques, MS is essentially a clinical problem and can be diagnosed using clinical and paraclinical criteria""^[28]

At this moment, both definitions are currently used by each of their supporters and the relationship among them is not well documented.

Current definitions

The list of diseases included in the MS-spectrum is not closed because no formal definition of MS is normally given. For example, the World Health Organization does not give any explicit definition with ICD-10 MS entry [2]. In ICD-9 it used to say "chronic disease characterized by presence of numerous areas of demyelination in the central nervous system with symptoms such as weakness, incoordination, paresthesis, and speech disturbances"[3].

The Unified Medical Language System also gives very loose definitions of MS [4]. The Medline medical dictionary defines it as "a demyelinating disease marked by patches of hardened tissue in the brain or the spinal cord and associated especially with partial or complete paralysis and jerking muscle tremor" [5]. It uses the anatomical hallmark of the lesions, but also imposes the existence of clinical problems (paralysis and jerking muscle tremor)

Assuming a definition as weak as the previous ones, several diseases could be included inside the MS-spectrum. Other authors use a definition for MS based in its clinical course [6]. Clinical definitions refer to the lesions and their location, but not to the nature of the lesions and this kind of definitions are potentially heterogeneous. As with any definition, patients have to be considered non-affected until the definition conditions are satisfied.

See also

• Demyelinating disease
• Pathophysiology of multiple sclerosis
• The Myelin Project

References

Multiple sclerosis and other demyelinating diseases of CNS (G35–G37, 340–341) Signs and symptoms Ataxia · Depression · Diplopia · Dysarthria · Dysphagia · Fatigue · Incontinence · Neurological fatigue · Nystagmus · Optic neuritis · Pain · Uhthoff's phenomenon · Dawson's fingers Diagnosis and evolution following McDonald criteria · Poser criteria · EDSS · Clinically isolated syndrome Investigation Pathophysiology · Experimental autoimmune encephalomyelitis Treatment Interferon beta-1a  · Interferon beta-1b · Glatiramer acetate · Mitoxantrone · Natalizumab · Fingolimod · Therapies under investigation Borderline forms Acute disseminated encephalomyelitis · Balo concentric sclerosis · Neuromyelitis optica · Marburg multiple sclerosis · Schilder's disease · Tumefactive multiple sclerosis (Guillain-Barré syndrome and CIDP are PNS) Other List of people with multiple sclerosis · List of multiple sclerosis organizations M: CNS anat(n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco(m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug(N1A/2AB/C/3/4/7A/B/C/D)

Pathology of the nervous system, primarily CNS (G04–G47, 323–349) Inflammation Brain Encephalitis (Viral encephalitis, Herpesviral encephalitis) · Cavernous sinus thrombosis · Brain abscess (Amoebic) Spinal cord Myelitis: Poliomyelitis · Demyelinating disease (Transverse myelitis) · Tropical spastic paraparesis · Epidural abscess Both/either Encephalomyelitis (Acute disseminated) Meningoencephalitis Brain/ encephalopathy Degenerative Extrapyramidal and movement disorders Basal ganglia disease: Parkinsonism (PD, Postencephalitic, NMS) · PKAN · Tauopathy (PSP) · Striatonigral degeneration · Hemiballismus · HD · OA Dyskinesia: Dystonia (Status dystonicus, Spasmodic torticollis, Meige's, Blepharospasm) · Chorea (Choreoathetosis) · Myoclonus (Myoclonic epilepsy) · Akathesia Tremor (Essential tremor, Intention tremor) · Restless legs · Stiff person Dementia Tauopathy: Alzheimer's (Early-onset) · Frontotemporal dementia/Frontotemporal lobar degeneration (Pick's, Dementia with Lewy bodies) Multi-infarct dementia Mitochondrial disease Leigh's Demyelinating autoimmune (Multiple sclerosis, Neuromyelitis optica, Schilder's disease) · hereditary (Adrenoleukodystrophy, Alexander, Canavan, Krabbe, ML, PMD, VWM, MFC, CAMFAK syndrome) · Central pontine myelinolysis · Marchiafava-Bignami disease · Alpers' disease Episodic/ paroxysmal Seizure/epilepsy Focal · Generalised · Status epilepticus · Myoclonic epilepsy Headache Migraine (Familial hemiplegic) · Cluster · Tension Cerebrovascular TIA (Amaurosis fugax, Transient global amnesia) Stroke (MCA, ACA, PCA, Foville's, Millard-Gubler, Lateral medullary, Weber's, Lacunar stroke) Sleep disorders Insomnia · Hypersomnia · Sleep apnea (Obstructive, Ondine's curse) · Narcolepsy · Cataplexy · Kleine-Levin · Circadian rhythm sleep disorder (Advanced sleep phase syndrome, Delayed sleep phase syndrome, Non-24-hour sleep-wake syndrome, Jet lag) CSF Intracranial hypertension (Hydrocephalus/NPH, Idiopathic intracranial hypertension) · Cerebral edema · Intracranial hypotension Other Brain herniation · Reye's · Hepatic encephalopathy · Toxic encephalopathy Spinal cord/ myelopathy Syringomyelia · Syringobulbia · Morvan's syndrome · Vascular myelopathy (Foix-Alajouanine syndrome) · Spinal cord compression Both/either Degenerative SA Friedreich's ataxia · Ataxia telangiectasia MND UMN only: PLS · PP · HSP LMN only: PMA · PBP (Fazio-Londe, Infantile progressive bulbar palsy) · Spinal muscular atrophies (SMA, SMARD1, SBMA, SMAX2, SMA-PCH) both: ALS M: CNS anat(n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp noco(m/d/e/h/v/s)/cong/tumr, sysi/epon, injr proc, drug(N1A/2AB/C/3/4/7A/B/C/D)