Spontaneous recovery in ADEM?

http://jnnp.bmj.com/content/75/suppl_1/i22.full

J Neurol Neurosurg Psychiatry 2004;75:i22-i28 doi:10.1136/jnnp.2003.034256

INFLAMMATORY/POST-INFECTIOUS ENCEPHALOMYELITIS

L Bennetto, N Scolding

Author Affiliations: Institute of Clinical Neurosciences, Department of Neurology, University of Bristol, Frenchay Hospital, Bristol, UK

Spontaneous recovery is the rule, usually over a course of weeks to months. ADEM tends to have a more severe initial course but much better ultimate recovery than MS. Historically fatal disease was common, with reported mortality rates as high as 30–50% as recently as 1948 in European children with post-vaccination ADEM. The outlook this millennium appears much brighter, with three recent studies encompassing 150 children with ADEM reporting no deaths. One of these studies followed up their 35 cases for a mean 5.8 years and found that the majority completely recovered in a few weeks. Twenty patients had no long term impairment; permanent neurological deficits included motor dysfunction (six patients, severe in three), cognitive impairment (four patients), visual loss (four patients), and behavioural problems (four patients). Epilepsy developed in three patients but persisted in only one with extended follow up. A recent study of 40 adult patients with ADEM reported two mortalities, suggesting that adult ADEM may presently have a slightly worse prognosis than childhood ADEM.

Treatment options

Corticosteroids are widely considered to be an effective first line treatment for ADEM. Intravenous methylprednisolone 1 g daily for at least three days is advised. While expert opinion and several convincing reports support this regimen, the natural history of ADEM of course features spontaneous improvement, and it is difficult therefore to be absolutely certain of its benefits. The recent trend towards improved survival in reported case series of ADEM may, however, reflect increased use of corticosteroids, intravenous methylprednisolone in particular. The rationale for corticosteroid use is their ability to reduce inflammation, decrease oedema, and seal the blood–brain barrier, which should decrease the further influx of active immune cells and humoral factors, contributing to demyelination. In some cases, cessation of steroid treatment has been followed by a relapse, possibly forming the basis of MDEM. As a relapse suggestive of MDEM is most likely shortly after ADEM it would seem prudent to prescribe a 1–2 month oral prednisolone taper.

Plasma exchange is recommended in patients who respond poorly to intravenous corticosteroids. There have also been several reports of impressive responses to plasma exchange; however, some of these have been confounded by the co-administration of corticosteroids and cyclophosphamide. More importantly a randomised, controlled, crossover trial of true versus sham plasma exchange for attacks of severe CNS demyelination resistant to corticosteroid treatment in 22 patients showed that 42% of patients had moderate or greater neurological improvement in the plasma exchange arm compared with just 6% of the patients receiving sham treatment (statistically significant). Although this study only had one patient with ADEM, the other conditions treated under the remit of “severe CNS demyelination”—MS, Marburg variant MS, acute transverse myelitis, neuromyelitis optica—are sufficiently similar and occasionally indistinguishable from ADEM in the acute phase to represent a reasonable rationale for treatment at present. This study used a course of seven plasma exchanges over 14 days, but improvement is frequently observed after the first exchange.

Intravenous immunoglobulin (IVIG) has also been used with success in a few cases of ADEM. While the evidence behind its use in ADEM is probably weaker than that of plasma exchange, there are several neuro-inflammatory conditions where IVIG has a proven effect and is often considered a more convenient alternative to plasma exchange. At present it should be reserved for ADEM that fails to respond to corticosteroid treatment and where plasma exchange is contraindicated or impractical. There have been suggestions based on subtle pathogenetic differences that IVIG may be preferable to plasma exchange in cases of post-vaccination encephalomyelitis, but this is not proven. Intravenous cyclophosphamide has also been used in the past with some apparent success but has not gained widespread recommendation.

In severe cases of ADEM, and particularly acute haemorrhagic leucoencephalomyelitis, cerebral oedema can occur and should be treated with combinations of mannitol and hyperventilation. If these conservative measures fail then more drastic measures such as craniotomy can be considered.

ADEM has been known to relapse into MDEM following routine vaccinations and it would seem sensible to avoid vaccinations (or other immune stimulation) for at least six months following a diagnosis of ADEM.

Article discussing Opercular Syndrome in ADEM

http://pn.bmj.com/content/10/2/109.full

Pract Neurol 2010;10:109-111 doi:10.1136/jnnp.2010.206110
The groom who could not say “I do”

A 25-year-old North American man came to Portugal on honeymoon. The week before, he had developed slowly progressive difficulty with both speaking and swallowing. At his wedding ceremony in the USA 2 days earlier, he had not been able to speak, saying “I do” using gestures, and could barely eat his own wedding cake. He deteriorated further after the wedding and by the following day he was unable to swallow.

Ten days before the onset of these symptoms, he had suffered a flu-like illness that resolved spontaneously over a couple of days. He was previously healthy, not taking any medication and not using any illicit drugs.

On examination, he was calm and alert, capable of following commands and could read and write which facilitated communication. He was anarthric, making only effortful guttural sounds and required nasogastric tube feeding because of severe dysphagia. He had bilateral ptosis and bilateral facial weakness. However, while his voluntary mouth opening was limited, it was normal when he yawned. His palatal movement was reduced but his gag reflex was intact, as was his jaw jerk. He could not cough voluntarily but had a reflex cough. He was unable to protrude or move his tongue from side to side. Ocular movements were normal and he had normal strength in his arms and legs with symmetrical tendon reflexes. He was apyrexial and haemodynamically stable. The rest of his general examination was normal.

FTD ALS overlap

J Mol Neurosci. 2011 Nov;45(3):656-62. doi: 10.1007/s12031-011-9636-x. Epub 2011 Oct 5.

Clinical phenomenology and neuroimaging correlates in ALS-FTD.

Lomen-Hoerth C.

Source

Department of Neurology, University of California, San Francisco, 350 Parnassus Avenue, Suite 500, San Francisco, CA 94117, USA. catherine.lomen-hoerth@ucsf.edu

Abstract

The overlap of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) has been well documented in FTD patients with co-morbid motor neuron degeneration and in ALS patients with frontotemporal dysfunction. Up to 15% of FTD patients and 30% of ALS patients experience the overlap syndrome. The syndrome may be difficult to identify since patients often present either to a neuromuscular clinic or a memory disorder's center, each which may have limited expertise in the other specialty. Survival is greatly impacted for both disorders in the co-morbid condition, making identification of this syndrome critical. The clinical characteristics of the overlap syndrome with new diagnostic criteria will be discussed along with screening strategies, including the UCSF Screening battery and clinical neurophysiology techniques. Treatable mimics of this disorder will also be described and management techniques. Neuroimaging findings will be summarized, which show that the frontotemporal impairment in ALS patients lies on a continuum. Identification of the overlap syndrome also provides a unique opportunity to study very early signs of FTD and conversely, very early signs of ALS, to gain greater insight into both disorders.

Postsynaptic potentials

http://xa.yimg.com/kq/groups/6985863/1696231188/name/Neurophysiologic%20Basis%20of%20EEG-Olejniczak2006.pdf

http://jn.physiology.org/content/102/5/3046.full

Questions on EEG

1. What is electricity?
2. How do we measure it? 
3. What do we measure when we put an electrode on the scalp?
4. Obviously there is no movement of electrons across the electrodes, so it must be measuring some sort of a field. What is meant by electric field, how is it different from electromagnetic field and electrostatic field?

From www.physicsclassroom.com

Structure of matter

Not only do electrostatic occurrences permeate the events of everyday life, without the forces associated with static electricity, life as we know it would be impossible. Electrostatic forces - both attractive and repulsive in nature - hold the world of atoms and molecules together in perfect balance. Without this electric force, material things would not exist. Atoms as the building blocks of matter depend upon these forces. And material objects, including us Earthlings, are made of atoms and the acts of standing and walking, touching and feeling, smelling and tasting, and even thinking is the result of electrical phenomenon. Electrostatic forces are foundational to our existence.

Boyle's studies (middle to late 1600s) of gaseous substances promoted the idea that there were different types of atoms known as elements. Dalton (early 1800s) conducted a variety of experiments to show that different elements can combine in fixed ratios of masses to form compounds. Dalton subsequently proposed one of the first theories of atomic behavior that was supported by actual experimental evidence.

English scientist J.J. Thomson's cathode ray experiments (end of the 19th century) led to the discovery of the negatively charged electron and the first ideas of the structure of these indivisible atoms. Thomson proposed the Plum Pudding Model, suggesting that an atom's structure resembles the favorite English dessert - plum pudding. The raisins dispersed amidst the plum pudding are analogous to negatively charged electrons immersed in a sea of positive charge.

Nearly a decade after Thomson, Ernest Rutherford's famous gold foil experiments led to the nuclear model of atomic structure. Rutherford's model suggested that the atom consisted of a densely packed core of positive charge known as the nucleus surrounded by negatively charged electrons. While the nucleus was unique to the Rutherford atom, even more surprising was the proposal that an atom consisted mostly of empty space. Most the mass was packed into the nucleus that was abnormally small compared to the actual size of the atom.

Neils Bohr improved upon Rutherford's nuclear model (1913) by explaining that the electrons were present in orbits outside the nucleus. The electrons were confined to specific orbits of fixed radius, each characterized by their own discrete levels of energy. While electrons could be forced from one orbit to another orbit, it could never occupy the space between orbits.

Bohr's view of quantized energy levels was the precursor to modern quantum mechanical views of the atoms. The mathematical nature of quantum mechanics prohibits a discussion of its details and restricts us to a brief conceptual description of its features. Quantum mechanics suggests that an atom is composed of a variety of subatomic particles. The three main subatomic particles are the proton, electron and neutron. The proton and neutron are the most massive of the three subatomic particles; they are located in the nucleus of the atom, forming the dense core of the atom. The proton is charged positively. The neutron does not possess a charge and is said to be neutral. The protons and neutrons are bound tightly together within the nucleus of the atom. Outside the nucleus are concentric spherical regions of space known as electron shells. The shells are the home of the negatively charged electrons. Each shell is characterized by a distinct energy level. Outer shells have higher energy levels and are characterized as being lower in stability. Electrons in higher energy shells can move down to lower energy shells; this movement is accompanied by the release of energy. Similarly, electrons in lower energy shells can be induced to move to the higher energy outer shells by the addition of energy to the atom. If provided sufficient energy, an electron can be removed from an atom and be freed from its attraction to the nucleus.

Summary:

• All material objects are composed of atoms. There are different kinds of atoms known as elements; these elements can combine to form compounds. Different compounds have distinctly different properties. Material objects are composed of atoms and molecules of these elements and compounds, thus providing different materials with different electrical properties.
• An atom consists of a nucleus and a vast region of space outside the nucleus. Electrons are present in the region of space outside the nucleus. They are negatively charged and weakly bound to the atom. Electrons are often removed from and added to an atom by normal everyday occurrences. These occurrences are the focus of this Static Electricity unit.
• The nucleus of the atom contains positively charged protons and neutral neutrons. These protons and neutrons are not removable or perturbable by usual everyday methods. It would require some form of high-energy nuclear occurrence to disturb the nucleus and subsequently dislodge its positively charged protons. These high-energy occurrences are fortunately not an everyday event. One sure truth of this unit is that the protons and neutrons will remain within the nucleus of the atom. Electrostatic phenomenon can never be explained by the movement of protons.

Concepts in Static Electricity

Rubbing two objects against each other brings the electron fields of the atoms in each close to each other. Electron affinity varies amongst molecules. If there is a significant difference in this property between the two objects being rubbed against each other, then electrons will be transferred. This will result in a charge on the surface of both objects. The charge will obviously be of opposite polarity. It will also be equal in magnitude. This is known as the "Law of conservation of charge". A triboelectric series is the order in which objects are arranged according to the degree of electron affinity.

Dorsal digital expansion

Finger extension - DDE - 'Diamond' complex
1) Axis - Extensor digitorum tendon
2) Proximal wing tendon - interossei
3) Distal wing tendon - lumbricals
See Gray's Anatomy 37Ed Fig 5.70 5.71 5.83

Immunocompromising conditions

Immunocompromising Conditions (List from eMedicine)
a) Congenital
b) Acquired
c) Iatrogenic / self inflicted

a) Congenital Conditions

These most commonly affect the fetus and newborn. Hemoglobinopathy may be noted.
Syndromes

• Partial albinism with immunodeficiency (Griscelli) syndrome^{[2, 3]}
• Hemorrhagic hereditary telangiectasia (Rendu-Osler disease)^[4]
• Immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome
• Kabuki syndrome
• Partial albinism, immunodeficiency, and progressive white matter disease (PAID) syndrome
• Autoimmune polyendocrinopathy syndrome type 1
• Rubinstein-Taybi syndrome^[5]
• Hermansky-Pudlak-2 syndrome
• CHARGE syndrome^[6]
• Other dysmorphology or immunodeficiency syndromes
• Stromal interaction molecule 1 mutation^[7]

B-cell defects^[8]

• Antibody deficiency with transcobalamin II deficiency
• Antibody deficiency with normal or high immunoglobulin (Ig) levels
• Common variable immunodeficiency
• IgG heavy-chain deletion
• IgG subclass deficiency
• Kappa-chain deficiency
• Organic cation transporter 2 deficiency
• Selective IgA deficiency
• Selective IgM deficiency
• Selective antipolysaccharide antibody deficiency
• Transient hypogammaglobulinemia of infancy or early childhood
• Thymoma with agammaglobulinemia
• X-linked (Bruton) agammaglobulinemia
• X-linked hyper-IgM syndrome
• X-linked hypogammaglobulinemia with growth hormone deficiency

Combined B-cell and T-cell defects

• Adenosine deaminase deficiency
• Artemis deficiency
• Ataxia-telangiectasia syndrome
• Bare lymphocyte syndrome (major histocompatability complex class I/II deficiency)
• DOCK8 mutations^[9]
• Interleukin (IL)-2R alpha or gamma deficiency
• Intestinal lymphangiectasia
• Janus kinase 3 (JAK3) deficiency
• Nuclear factor-kappaB essential modifier (NEMO) deficiency (Dupuis-Girod, 2002; Courtois, 2006; Smahi, 2002; Zonana, 2000)
• Nijmegen breakage syndrome
• Omenn syndrome
• Purine nucleoside phosphorylase deficiency
• Recombination activation gene (RAG) 1 or 2 deficiency
• Reticular dysgenesis
• Swiss-type severe combined immunodeficiency
• T-cell receptor deficiency
• Wiskott-Aldrich syndrome^[10]
• X-linked lymphoproliferative syndrome
• X-linked severe combined immunodeficiency
• Zeta-associated protein of 70 kDa (ZAP-70) tyrosine kinase deficiency

T-cell defects

• Biotin-dependent multiple carboxylase deficiency
• Chronic mucocutaneous candidiasis
• DiGeorge (velocardiofacial) syndrome
• Fas defect
• Nezelof syndrome
• Short-limbed dwarfism or cartilage-hair hypoplasia

Macrophage, cytokine, and miscellaneous defects

• Mendelian susceptibility to mycobacterial diseases (MSMD)
  

  • Interferon-gamma deficiency
  • Interferon-gamma receptor I or II deficiency
  • IL-12 deficiency
  • IL-12 receptor deficiency
  • STAT1 mutations
  • NEMO
  • CYBB
• IL-1 receptor–associated kinase 4 (IRAK4) deficiency
• MYD88 deficiency
• Toll-like receptor 5 mutations
• Apolipoprotein L-I deficiency
• UNC-93B deficiency
• Toll-like receptor 3 mutations
• TRIF and TRAF3 mutations
• Plasminogen activator inhibitor-1 4G/4G promoter genotype
• Anti-interferon-gamma antibodies
• IL-18 polymorphisms
• RANTES promoter gene polymorphisms^[11]
• Deficiency of chemokine receptor CCR5^{[12, 13]}
• Toll-like receptor 4 mutations
• IL-8 RA (chemokine CXC motif receptor 1 [CXCR1]) mutations
• CXCR4 mutations (Whim syndrome)
• STAT 5 mutations
• NOD2 gene polymorphisms
• IL-6 polymorphisms
• Activating killer immunoglobulinlike receptor gene polymorphisms
• Dectin-1 deficiency
• CARD9 mutations
• Polymorphisms in cytokine-inducible SRC homology 2 domain protein (CISH)
• Polymorphisms in Mal/TIRAP and Interleukin-10
• Autoantibodies against IL-6^[14]
• Polymorphisms in the IL-8 promoter gene^[15]
• IL-12 receptor deficiency (Vinh, 2011)

Phagocyte deficiency or dysfunction

• Chediak-Higashi syndrome
• Chronic granulomatous disease
• Chronic idiopathic neutropenia
• Cyclic neutropenia
• Glycogen storage disease 1b
• Hyper-IgE/recurrent infection (Job) syndrome (Janus kinase protein tyrosine kinase 2 [Tyk2], signal transducer and activator of transcription [STAT] 3, and STAT 1 mutations)^[16]
• Kostmann syndrome
• Leukocyte adhesion deficiency (including CD11 or CD18 deficiency)
• Myeloperoxidase deficiency
• Neutrophil actin dysfunction
• Papillon-Lefèvre syndrome
• Specific granule deficiency
• Shwachman-Diamond syndrome

Complement deficiencies (Ram, 2010)

• Mannose-binding lectin (Mannan-binding protein) deficiency^{[17, 18]}
• Deficiencies of C1q, C1r, C1rs, C4, C2, C3, or C5-9
• Deficiencies of factor D, factor P, factor I, factor H, or properdin
• Ficolin-3 (H-ficolin) deficiency^[19]

Other conditions

• Asplenia^[20]
• Ciliary dyskinesia, Kartagener syndrome, and other disorders
• Galactosemia and other metabolic conditions
• Lymphedema (congenital)
• Trisomy 21 and other genetic disorders
• Other anatomic defects (eg, midline dermal sinus, Mondini defect of the inner ear, fistulae, cysts, duplications, meningeal defects, iron overload, decreased sensation)

b) Acquired Conditions

These conditions may interfere directly with the immune system or may disrupt barrier function.

• Malnutrition
• HIV infection: Although human immunodeficiency virus (HIV) infection is a considerable cause of immunodeficiency worldwide, immunocompromise is most likely to result from common problems, including asthma, diabetes, malnutrition, and cancer, among others.
• Trauma
  

  • Burns
  • Lacerations and abrasions
• Medical conditions
  

  • Collagen vascular
  • GI tract
  • Hematologic or oncologic
  • Hepatic
  • Metabolic
  • Pregnancy
  • Pulmonary, particularly asthma and cystic fibrosis (CF)
  • Renal
  • Skin and mucous membrane
  • Viral infections (eg, cytomegalovirus [CMV] infection,^[21] measles)
  • Other anatomic or physiologic problems (eg, fistulae, cysts, obstructions, iron overload, decreased sensation)
• Acquired asplenia (Ram, 2010)
• Acquired lymphedema
• Other conditions that injure or bypass barrier function
  

  • Parasitic infections
  • Animal and insect bites or scratches

c) Iatrogenic or Self-inflicted Conditions

These conditions may directly interfere with the immune system or may disrupt barrier function.
Use of drugs and/or therapies (eg, radiation therapy), which may interfere with normal flora, decrease gastric acidity and ciliary motility, and be directly immunomodulating^[22]
Trauma

• Injections (eg, insulin injections, intravenous [IV] drug use, others)
• Operative and other incisions
• Vascular, osseous, tracheal, gastric, bladder, joint, peritoneal, wound, or ventricular access or drainage devices
• Internal foreign bodies
• Major surgery^[23]

Treatment

• For leukemia or lymphoma
• Bone marrow or stem-cell transplantation
• Solid organ transplantation (Yin, 2011)
• Therapy for autoimmune or inflammatory disorders
• TNF-alpha inhibitors^[24]
• Monoclonal antibodies and related small molecules

Wilsons disease with behavioral problems and isolated midbrain lesions

Question - can patients with Wilsons disease present with isolated psychopathic (especially abnormal sexual) behavior?
Yes - see the range of behavioral manifestations in Wilsons http://neuro.psychiatryonline.org/data/Journals/NP/3960/08JNP81.PDF , http://www.ncbi.nlm.nih.gov/pubmed/7872138 , http://books.google.co.in/books?id=Ag5710EHVpAC&pg=PA23&lpg=PA23&dq=wilsons+disease+substance+abuse&source=bl&ots=63ocZTdPcm&sig=L0H9HbqTcqwIGw-NFNk6j1iklvw&hl=en&sa=X&ei=pCyiUKH4AY7trQf0m4DoBw&ved=0CE4Q6AEwBQ#v=onepage&q=wilsons%20disease%20substance%20abuse&f=false

Question - can patients with Wilsons disease have changes only in midbrain (no changes in putamen / lenticular nuclei)
Yes - see the range of MRI abnormalities in Wilsons http://www.ncbi.nlm.nih.gov/pubmed/17894614 , http://www.ncbi.nlm.nih.gov/pubmed/20437536 , http://www.ncbi.nlm.nih.gov/pubmed/16752136

Question - can patients with Wilsons disease have only abnormality of elevated 24 hour urinary copper?
Yes - see the range of biochemical abnormalities and guidelines for diagnosis of Wilsons disease http://www.uptodate.com/contents/tests-used-in-the-diagnosis-of-wilson-disease , http://guidelines.gov/content.aspx?id=13004

Wilsons Behavioral Problems 1995 article

http://www.ncbi.nlm.nih.gov/pubmed/7872138

Adv Neurol. 1995;65:171-8.
Psychiatric and behavioral abnormalities in Wilson's disease.
Akil M, Brewer GJ.Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, Pennsylvania 15213.

From the literature and our experience, a relatively consistent picture of psychiatric and behavioral abnormalities in Wilson's disease emerges. The essential elements of this picture are as follows: 

1. Psychiatric and behavioral abnormalities are frequent manifestations of WD. The estimates range from 30% (18) to 100% (2) of symptomatic patients. As Wilson himself was the first to state in reference to "mental change," "its importance should not be underestimated." 

2. Psychiatric and behavioral abnormalities are often the initial manifestations of WD. Two thirds of our patients first presented with psychiatric symptoms and one third received psychiatric treatment before the diagnosis of WD was made. In the early stages of the disease, when psychiatric and behavioral symptoms predominate, the diagnosis is often missed. Of our 124 patients, WD was diagnosed in only one during this phase. Until the psychiatric presentation of WD is recognized, and the disease is included in the differential diagnosis of psychiatric symptoms, its diagnosis will be missed or delayed. In our patients, and others' (13,15), the delay in diagnosis ranged from 1 to 5 years. Such a delay is particularly tragic as favorable outcome depends upon early discovery. 

3. The most common of the psychiatric and behavioral manifestations of WD include: personality changes such as irritability and low threshold to anger, depression sometimes leading to suicidal ideation and attempts, deteriorating academic and work performance that is present in almost all neurologically affected patients. We (1) have also observed, as did Scheinberg and Sternlieb (2) that WD patients exhibit increased sexual preoccupation and reduced sexual inhibition. Finally, cognitive impairment, psychosis, anxiety, and other psychiatric disorders, although less frequent, also occur. 

4. Some of the psychiatric and behavioral symptoms are reversible with WD-specific therapy, whereas others are not. We are impressed with the frequency with which the behavioral and "cognitive" symptoms are reversed over 1 to 2 years of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Violence and psychopathic behavior presentation

Neurological and systemic conditions listed on various websites including Crime Times

1. Temporal lobe/ amygdala lesions - tumors, HSE
2. Toxins like organophosphates and carbamates
3. Thyroid disorders
4. Wilsons disease, Huntington's disease, hyperparathyroidism, vitamin deficiencies, limbic encephalitis, and sleep disorders

Conditions associated with sex offences - Tourette's syndrome (anecdotal response of abnormal sexual behavior to pimozide) and Wilson's disease

Retinal Vasculitis with CNS disease

In a patient with retinal vasculitis, it is useful to know the following:
1) Type of retinal vessels involved - arterioles, venules, capillaries
2) CSF study normal or abnormal
3) MRI Brain normal, vasculitis, white matter changes, ventricular enlargement

Identification of retinal vessels involved 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855661/

Retinal vasculitis affecting predominantly the veins (phlebitis) has been described in association with Behçet's disease, tuberculosis, sarcoidosis, multiple sclerosis, pars planitis, retinal vasculitis associated with tuberculoprotein hypersensitivity (Eales' disease), human immunodeficiency virus infection (HIV). Retinal arteritis is more commonly seen in acute retinal necrosis, idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and systemic vasculitides such as SLE, polyarteritis nodosa, and Wegener's granulomatosis, Churg-Strauss syndrome and cryoglobulinemia.

List of causes of retinal vasculitis (Uptodate)

Systemic disorders

Behcet's disease

Granulomatosis with polyangiitis (Wegener's)

Sarcoidosis

Relapsing polychondritis

Systemic lupus erythematosus

Giant cell arteritis

Polyarteritis nodosa

Multiple sclerosis

Whipple's disease

Crohn's disease

HLA-B27 associated conditions

Infectious disorders

Toxoplasmosis

Tuberculosis

Syphilis

Herpes simplex

Herpes zoster

Acute retinal necrosis

Cytomegalovirus

Coccidiomycosis

Hepatitis

Amoebiasis

Candidiasis

Leptospirosis

Ricketsia

Brucellosis

Lyme disease

Human immunodeficiency virus

Toxocariasis

Ocular disorders

Birdshot retinochoroidopathy

Pars planitis

Eale's disease

Retinal arteriolitis

Behcet's sine systemic disease

Sympathetic ophthalmia

Classification of retinal vasculitis by involved vessel

Disease	Primary vessel involved
Polyarteritis nodosa	Muscular arteries
Granulomatosis with polyangiitis (Wegener's); giant cell arteritis	Medium to small arteries
Systemic lupus erythematosus	Small arteries
Whipple's disease	Capillaries
Behcet's disease; sarcoidosis; multiple sclerosis	Veins
Crohn's disease; relapsing polychondritis	Arteries and veins
HLA-B27 associated conditions, such as ankylosing spondylitis	Variable or no involvement

EEG Questions

What is the electrical principle behind an EEG?

What is actually moving (?electrons), why is it moving, and how do we pick up the amount and direction of movement?

What is the relation between movement of electrons and electrical field?

What are the electrodes on the surface of the scalp actually picking up?

How is the electric field in scalp recording different from ECG?

What is really meant by potential difference?

Types of diabetic neuropathies

Symmetric

• Distal symmetric polyneuropathy.
• Autonomic neuropathy.
• Transient distal sensory neuropathy.
• Diabetic neuropathic cachexia (rare).

Asymmetric

• Diabetic amyotrophy (proximal diabetic neuropathy, diabetic lumbosacral radiculoplexopathy).
• Cranial neuropathy.
• Truncal radiculopathy.
• Isolated mononeuropathy.

Observations on role of IVIg in diabetic neuropathy

Acta Myol. 2003 Dec;22(3):97-103.
Intravenous immunoglobulin G is remarkably beneficial in chronic immune dysschwannian/dysneuronal polyneuropathy, diabetes-2 neuropathy, and potentially in severe acute respiratory syndrome.
Engel WK.

Abstract

Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy is an autoimmune peripheral-nerve and/or nerve-root disorder known to usually respond to intravenous immunoglobulin-G treatment. Benefit can involve any combination of motor-nerve fibers and large and small sensory-nerve fibers responsible for a progressively crippling, unbalancing, discomforting or painful disorder. "Diabetic neuropathy" is commonly considered untreatable. However, 81% of my 48 recently-summarized type-2 diabetes patients with polyneuropathy, adequately-treated with intravenous immunoglobulin-G, off-label, were relieved, sometimes completely, of various motor and sensory symptoms, including pain, thereby resembling Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy. Spinal fluid protein in them is often elevated, higher values seeming to auger a better intravenous immunoglobulin-G response. Continuing the improvement requires continuing the intravenous immunoglobulin-G treatment, indicating both intravenous immunoglobulin-G responsiveness and dependency. The intravenous immunoglobulin-G responsive type-2 diabetes polyneuropathy usually is dysschwannian, sometimes mainly dysneuronal intravenous immunoglobulin-G, the most beneficial and safest treatment, is costly, but if intravenous immunoglobulin-G-treatability of a dysimmune component of type-2 diabetes neuropathy is overlooked, dismissed or rejected, as commonly happens, other costs are high regarding the patient's worsening morbidity and disability, and resultant need for increased medical care. A novel intravenous immunoglobulin-G regimen effective for fragile patients is Two Non-Consecutive-Days Every Week, using 0.4 gm/kg body wt/day. Possible molecular mechanisms of intravenous immunoglobulin-G benefit are discussed. I propose that a) there is a higher incidence of Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy-like neuropathy in type-2 diabetes patients and in patients with a strong family history of type-2 diabetes, and b) the intravenous immunoglobulin-G-treatable neuropathy in type-2 diabetes can be brought on by the genetico-diabetoid-2 state. The genetic-metabolic milieu (but not necessarily glucose dysmetabolism per se.) of type-2 diabetes putatively predisposes to the presumably-dysimmune intravenous immunoglobulin-G-responsive polyneuropathy. In some of our patients, especially ones having a strong type-2 diabetes genetic background, the intravenous immunoglobulin-G-responsive neuropathy preceded the diagnosis of type-2 diabetes by 5-10 years. Accordingly, Chronic Immune Dysschwannian/Dysneuronal Polyneuropathy patients having a strong type-2 diabetes genetic background are designated "genetico-diabetoid-2 neuropathy" prior to their manifesting type-2 diabetes.

Intravenous immunoglobulin-G is herein suggested as a treatment for Severe Acute Respiratory Syndrome, a recent, and feared-repetitive, pandemic with many fatalities caused by a highly-contagious mutant coronavirus, for which there is no definitive treatment. Intravenous immunoglobulin-G might: a) combat a dysimmune component of Severe Acute Respiratory Syndrome, including the reactive cytokine-chemokine storm against respiratory tissues; b) contain some antibodies effective against the coronavirus non-specific components of Severe Acute Respiratory Syndrome; c) block host-cell receptors for the virus; and d) counteract secondary infections.

Diabetic Neuropathy

http://neuromuscular.wustl.edu/nother/diabetes.htm#da

Diabetes and Neuromuscular disorders

Symmetric neuropathies

• Chronic
• Distal sensory/autonomic
• Autonomic
• Sensory-motor
• Acute
• Painful
• Reversible

Asymmetric neuropathies

• Lumbosacral plexopathy
• Mononeuropathies
• Mononeuritis multiplex

Predisposition to immune PN

• CIDP
• ? Diabetic amyotrophy
• Perineuritis

Muscle infarction

Multifocal acquired demyelinating sensory and m... [Muscle Nerve. 1999] - PubMed - NCBI

Multifocal acquired demyelinating sensory and m... [Muscle Nerve. 1999] - PubMed - NCBI: 

Saperstein, D. S., Amato, A. A., Wolfe, G. I., Katz, J. S., Nations, S. P., Jackson, C. E., Bryan, W. W., Burns, D. K. and Barohn, R. J. (1999), Multifocal acquired demyelinating sensory and motor neuropathy: The Lewis–Sumner syndrome. Muscle Nerve, 22: 560–566.

We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.
'via Blog this'

Chronic Immune Demyelinating Neuropathies: Variants

http://neuromuscular.wustl.edu/antibody/pnimdem.html#variant

Acute onset β-Tubulin antibodies Childhood CNS features Diabetes IgM vs GM2 & GalNAc-GD1a Motor M-protein: IgM; IgG or IgA Multifocal Upper limb Perineuritis POEMS Sensory Subacute Typical

• Multifocal CIDP⁹
  • Nosology
    • Multifocal CIDP
    • Lewis-Sumner¹
    • MADSAM
    • Also see: Upper limb CIDP
  • Age range: 28 to 58 years
  • Weakness
    • Asymmetric
    • Distal > Proximal
    • Arms > Legs (78%)
    • Proximal syndrome: Occasional
      • Phrenic nerve: Diphragm weakness; Respiratory insufficiency
      • Suprascapular nerve: Infraspinatus ± Supraspinatus weakness
      • Other scattered distal & proximal muscles
  • Sensory loss: Distal; Pansensory; Rarely severe or disabling
  • Tendon reflexes: Focal loss
  • Course: Slowly progressive, or Relapsing-Remitting
  • Laboratory
    • Electrophysiology
      • Multifocal conduction block
      • Nerve conduction velocities: Variably slow
      • Distal latencies: Variably prolonged
    • CSF protein: High but usually < 100 mg/dL
    • IgM anti-GM1 antibodies: Never
    • MRI: Swollen nerves in brachial plexus with high T2 signal
    • Nerve pathology
      • ± Demyelination (Patchy)
      • Differential fascicular loss of axons
  • Treatment: Prednisone; HIG
  
  
• Multifocal upper limb CIDP^2,6
  • Male:Female = 1.9:1
  • Onset
    • Mean = 43 to 54 years; Range 9 to 75 years
    • Rarely childhood
    • Acute or Progressive
    • Distal
  • Clinical
    • Weakness
      • Onset: May be motor, sensory, or both; With reduced pain
      • Single or multiple upper extremity nerves
      • Distal > Proximal
      • Asymmetric > Symmetric
      • Monomelic or Bilateral
    • Sensory
      • Paresthesias or numbness early in most
      • Pain: 22%; Often localized to peripheral nerve territory
      • Sensory loss: Usually mild, distal; Often asymmetric
    • Tendon reflexes: Often reduced in involved limb(s)
    • Course
      • Progressive: To legs in 25%
      • Some stabilize or spontaneously resolve
    • Cranial nerves: 17%; Optic; III; VII
    • Rule out: Brachial neuritis
  • Laboratory
    • Anti-GM1 ganglioside antibodies: Uncommon
    • CSF protein
      • High in 40% to 72%
      • Mean 64 mg/dL; Range 21 to 128
    • Nerve conduction studies
      • Conduction block (100%): Proximal or Distal segments
      • Slowing 35%;
      • CMAP amplitude: Reduced (56%)
      • Abnormal SNAPs: Some patients; Up to 83%
      • Leg involvement: 34%
    • MRI
      • Usually normal
      • May have brachial plexus lesions
  • Treatment
    • Response to Prednisone or HIG in some (> 50%)
    • Often less recovery than with generalized CIDP
  
  
• Motor predominant CIDP ³⁶
  • Clinical
    • Onset
      • Age: 8 to 24 years
      • Weakness: Progressive over 1 to 6 months
    • Weakness
      • Distal > Proximal
      • Symmetric
      • Arm predominant or Arms & Legs
      • May be exacerbated by heat (Uhthoff-like phenomenon)
    • Sensory exam: Normal
    • Tendon reflexes: Diffusely absent
  • Laboratory
    • Nerve conduction studies
      • Motor: Distal & F-wave latency long; Conduction block; NCV slowed (17 to 33 M/s
      • Sensory: Normal or reduced SNAP amplitudes
    • CSF: Protein high
    • GM1 antibodies: Not present
  • Differential diagnosis: Multifocal motor neuropathy
  
  
• Sensory CIDP
  • Clinical
    • Sensory
      • Loss: Distal predominant; Pansensory or Small fiber
      • Pain
    • Motor: Normal or minimal distal weakness
    • Tendon reflexes: Normal or Reduced
  • Electrophysiology (NCV): Motor & Sensory demyelination
    • Motor
      • Conduction block
      • NCV: Slow
      • Distal latency: Long
    • Sensory: Slow NCV
  • Treatment: Poor response to prednisone or HIG
  
  
• Childhood CIDP
  • Prevalence: ~ 1 in 300,000; Male > Female
  • Preceding infections or vaccinations: 54%
  • Onset: Childhood to Teens; Rarely infancy
  • Course: Several patterns
    • Monophasic: 25%
      • Peak disability < 3 months
      • Off medications in < 1 year
    • Chronic
      • Persistent weakness & disability
      • Require continued immunosuppression
    • Acute onset: 25%
    • Relapsing: Often treatment related
  • Clinical patterns
    • Overall
      • Typical CIDP
      • Upper limb CIDP
      • Motor CIDP
    • Weakness: Proximal + Distal; Usually symmetric
    • Sensory loss: Pansensory; Distal; Symmetric
    • Tendon reflexes: Reduced or Absent
    • Other: Rare clinical CNS features
  • Disease Associations
    • Comparison with adult CIDP: Less with M-proteins & Diabetes
    • CNS changes: Rarely reported¹⁹
    • Other systems: Renal; Hearing²⁸
  • Prognosis
    • Better for remission with relatively rapid onset
    • Worse: Axonal loss
  • Laboratory
    • Pathology
      • Similar to adult CIDP
      • Chronic cases may have prominent demyelinating features
    • MRI: Gadolinium enhancement of roots very common; Occasional CNS changes
    • Nerve conduction: Similar to adult CIDP
  • Treatment
    • Corticosteroids: Response in > 90%
    • IVIg: Response in > 80%
    • Methotrexate: 2nd line treatment
  
  
• CIDP + IgM M-protein vs β-tubulin
  • Weakness: Slowly progressive; Asymmetric
  • Hyporeflexia
  • Poor response to prednisone
  • Antigenic epitope: β-tubulin amino acids 301-314
  
  
• CIDP associated with IgG or IgA M-protein
  • Similar clinical syndrome to typical CIDP
  • Weakness: Slowly progressive; Symmetric
  • Partial response to immunotherapy
  
  
• CIDP + Diabetes mellitus⁸
  • Patient characteristics: Most similar to CIDP alone
  • Differences from CIDP
    • Age: Older (67 years)
    • Symptoms: More gait imbalance
    • Electrodiagnostic: More axonal loss
    • Treatment: Less improvement
  
  
• CIDP: Acute onset³²
  • Onset: Progressive over days to weeks
  • Clinical
    • Weakness
      • Symmetric
      • Proximal & Distal
      • Uncommon: Face, Tongue, Eye movements, Respiratory failure
      • Less severe than GBS
    • Sensory loss: Distal
    • Tendon reflexes: Reduced
    • Course
      • Slower progression to nadir than GBS
      • Partial, but not complete improvement in strength over months
      • Treatment related exacerbations
        • Common
        • Time of first exacerbation: Median 18 days; Range 10 to 54 days
        • Especially > 8 weeks after onset
        • May occur ≥ 3 times
  • Laboratory
    • Electrodiagnostic
      • Prominent demyelinating features early in disease course
      • More slowing of motor nerve conduction velocity than GBS
      • Conduction block (30%)
      • EMG denervation (75%)
    • CSF protein: High
    • Antibodies: IgG anti-glycolipid uncommon
  
  
• CIDP: Subacute onset²³
  • Male > Female: 2 to 1
  • Onset
    • Age: Childhood or Adult
    • Progressive over 4 to 8 weeks
    • Antecedent infection (38%)
  • Clinical
    • Weakness (80%)
      • Symmetric (90%)
      • Proximal & Distal
    • Sensory loss (80%): Distal
    • Tendon reflexes: Reduced
    • Course
      • Improvement with corticosteroid treatment
      • Few relapses
  • Laboratory
    • Electrodiagnostic: Demyelination
      • NCV: Slow
      • Terminal latency: Prolonged (50%)
      • Conduction block: 50%
      • Temporal dispersion: 50%
      • Sensory: Absent SNAPs
    • CSF protein: High
    • Nerve biopsy
      • Demyelination in some: May require teased fibers to document
      • Inflammation: Epineurial; Some patients
  
  
• CIDP + CNS features¹⁹
  • Frequency: Rare patients with CNS features
  • Onset
    • Age: Adult or Childhood
    • Clinical: CNS or PNS features
  • CNS features
    • Ocular
      • Papilledema: Associated with high CSF protein
      • Visual loss: Optic atrophy
    • Myelopathy
      • Tendon reflexes may be brisk
      • r/o Spinal cord compression from enlarged nerve roots
    • Ataxia
    • Focal CNS myelin loss: 1 patient
      • CNS: Focal mass-like lesion
      • Weakness: Mild; Distal
      • Sensory loss: Mild vibration
      • Tendon reflexes: Normal
      • NCV: Slow; Long distal latency
    • Multiple sclerosis + CIDP²⁷
      • MS duration at onset: 4 to 22 years
      • Clinical
        • Weakness: Distal > Proximal;
        • Sensory loss: Distal; Pan-modal
        • Tendon reflexes: Reduced or Absent
      • CSF protein: > 120 mg/dL
      • Nerve conduction studies: Demyelinating neuropathy
      • Treatment: IVIg; Corticosteroids
  • Rule out: Late onset dysmyelination (MLD; Krabbe)
  • Treatment: Corticosteroids
• Perineuritis
  • Usually axonal neuropathy: Occcasional demyelinating neuropathy reported

Lacunar Syndromes

http://en.wikipedia.org/wiki/Lacunar_stroke

Charles Miller Fisher cadaver dissections 1965 publication in Neurology
200-800 micrometer penetrating arteries (?ref)
25% of all ischemic (?ref)
Location (?ref)

1. Putamen 37%
2. Thalamus 14%
3. Caudate 10%
4. Pons 16%
5. Capsule posterior limb 10%

The two proposed mechanisms are microatheroma and lipohyalinosis. At the beginning, lipohyalinosis was thought to be the main small vessel pathology, but microatheroma now is thought to be the most common mechanism of arterial occlusion (or stenosis). 

Each of the 5 classical lacunar syndromes has a relatively distinct symptom complex. Symptoms may occur suddenly, progressively, or in a fluctuating (e.g., the capsular warning syndrome) manner. Occasionally, cortical infarcts and intracranial hemorrhages can mimic lacunar infarcts, but true cortical infarct signs (such as aphasia, neglect, and visual field defects) are always absent.

Name	Location of infarct	Presentation
Pure motor stroke/hemiparesis (most common lacunar syndrome: 33-50%)	posterior limb of the internal capsule,basis pontis, corona radiata	It is marked by hemiparesis or hemiplegia that typically affects the face, arm, or leg of one side. Dysarthria, dysphagia, and transient sensory symptoms may also be present.
Ataxic hemiparesis (second most frequent lacunar syndrome)	posterior limb of the internal capsule,basis pontis, and corona radiata, red nucleus, lentiform nucleus, SCA infarcts, ACA infarcts	It displays a combination of cerebellar and motor symptoms, including weakness and clumsiness, on the ipsilateral side of the body. It usually affects the leg more than it does the arm; hence, it is known also as homolateral ataxia and crural paresis. The onset of symptoms is often over hours or days.
Dysarthria/clumsy hand (sometimes considered a variant of ataxic hemiparesis, but usually still is classified as a separate lacunar syndrome)	basis pontis, anterior limb or genu of internal capsule, corona radiata, basal ganglia, thalamus, cerebral peduncle	The main symptoms are dysarthria and clumsiness (i.e., weakness) of the hand, which often are most prominent when the patient is writing.
Pure sensory stroke	contralateral thalamus (VPL), internal capsule, corona radiata, midbrain	Marked by persistent or transient numbness, tingling, pain, burning, or another unpleasant sensation on one side of the body.
Mixed sensorimotor stroke	thalamus and adjacent posteriorinternal capsule, lateral pons	This lacunar syndrome involves hemiparesis or hemiplegia with ipsilateral sensory impairment

http://stroke.ahajournals.org/content/38/10/2706.full

The pathophysiological heterogeneity of ischemic stroke may be relevant to the development of acute-phase therapies because it is possible that what works for one subtype of stroke may work differently for another. Although no clinical stroke syndrome is absolutely pure with respect to pathophysiology, lacunar syndromes are the most homogeneous. Lacunar syndromes are usually due to a small subcortical infarct in the territory of a penetrating artery caused by in situ microatheroma or lipohyalinosis. Neurochemical studies suggest that subcortical ischemia may respond differently to hyperacute intervention than cortical ischemia. Subgroup analyses in a trial of a putative neuroprotective agent suggested the possibility of (an unexpected) benefit in patients with lacunar strokes. (Images Trial)