Case Definitions for Neuropsychiatric Syndromes in Systemic Lupus Erythematosus

Acute, inflammatory, and demyelinating syndrome of spinal roots, peripheral, and occasionally cranial nerves.

1. Progressive polyradiculoneuropathy, usually ascending and predominantly motor, which peaks usually within 21 days or less
2. Reflex loss
3. Symmetric, may involve the trunk and may cause respiratory failure.

Increased CSF protein without pleocytosis

The abnormalities are:

1. Conduction block in which the amplitude of compound muscle action potential diminishes with more proximal sites of nerve stimulation
2. F waves may be absent or prolonged
3. Slowing of conduction velocity
4. Prolongation of distal latencies

• Acute spinal cord disease
• Botulism
• Poliomyelitis and other infections
• Acute myasthenia gravis

By history, physical examination, electrophysiologic study, and CSF examination

Basic descriptors with these modifications

• Onset (acute or insidious)
• Course (acute - days/subacute - weeks/chronic - months to years)

Headache

Discomfort in the region of the cranial vault.

I. Migraine

Migraine without aura: Idiopathic, recurrent headache manifested by attacks lasting 4-72 hours. Typical characteristics are unilateral location, pulsating quality, moderate to severe intensity, aggravation by routine physical activity, and associated with nausea, vomiting, photo- and phonophobia. At least 5 attacks fulfilling the above criteria.

Migraine with aura: Idiopathic, recurrent disorder manifested by attacks of neurologic symptoms localizable to cerebral cortex or brain stem, usually gradually developing over 5-20 minutes and lasting less than 60 minutes. Headache, nausea, and/or photophobia usually follow neurologic aura symptoms directly or after an interval of less than 1 hour. Headache usually lasts 4-72 hours, but may be completely absent.

II. Tension headache (episodic tension type headache)

Recurrent episodes of headaches lasting minutes to days. Pain typically pressing/tightening in quality, of mild to moderate intensity, bilateral in location, and does not worsen with routine physical activity. Nausea is rare, but photophobia and phonophobia may be present. At least 10 previous headaches fulfilling these criteria.

III. Cluster headache

Attacks of severe, strictly unilateral pain, orbital, supraorbital, and/or temporal, usually lasting 15-180 minutes and occurring from at least once every other day up to 8 times per day. Associated with one or more of the following: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, forehead and facial sweating, myosis, ptosis, eyelid edema. Attacks occur in series for weeks or months ("cluster" periods) separated by remissions of usually months or years.

IV. Headache from intracranial hypertension (Pseudotumor cerebri, benign intracranial hypertension)

All of the following:

1. Increased intracranial pressure (200 mm H₂O) measured by lumbar puncture
2. Normal neurologic findings except for papilledema and possible nerve VI palsy
3. No mass lesion and no ventricular enlargement on neuroimaging
4. Normal or low protein and normal white cell count in CSF
5. No evidence of venous sinus thrombosis

V. Intractable headache, nonspecific

Exclusions:

• Aseptic meningitis (including drug-induced)
• Drug-induced pseudotumor cerebri (oral contraceptives, sulfonamides, trimethoprim, etc.)
• CNS infection
• Tumors and other structural lesions
• Low intracranial pressure
• Trauma
• Metabolic headache that remits with elimination of cause (carbon monoxide exposure)
• Withdrawal (caffeine, etc.)
• Seizure/postictal state
• Sepsis
• Intracranial hemorrhage or vascular occlusion

Associations:

• Cranial neuropathies
• Headache associated with abnormalities of the eye, ear, sinus, teeth, temporomandibular joint, or cervical spine

Ascertainment:

• History (duration, localization, photophobia, visual disturbance, weakness, numbness, tingling, response to analgesia, aura)
• Physical examination including fundoscopy
• Lumbar puncture when indicated
• Imaging when indicated
• Antiphospholipid antibodies when indicated

Record:

• Basic descriptors
• Type of headache

Neuropathy, Cranial

Disorder of sensory and/or motor function of a specific cranial nerve(s).

Diagnostic criteria:

Syndrome corresponding to specific nerve function:

I. Olfactory nerve: Loss of sense of smell, distortion of smell, and loss of olfactory discrimination

II. Optic nerve: Decrease or loss of visual acuity, diminished color perception, afferent pupillary defect and visual field deficits

III. Oculomotor nerve: Ptosis of the upper eyelid and inability to rotate eye upward, downward, or inward (complete lesion), and/or dilated nonreactive pupil and paralysis of accommodation (interruption of parasympathetic fibers only)

IV. Trochlear nerve: Extorsion and weakness of downward movement of affected eye

VI. Abducens nerve: Weakness of eye abduction

V. Trigeminal nerve: Paroxysm of pain in lips, gums, cheek, or chin initiated by stimuli in trigger zone (trigeminal neuralgia) and sensory loss of the face or weakness of jaw muscles

VII. Facial nerve: Unilateral or bilateral paralysis or facial expression muscles, impairment of taste, and hyperacusis (painful sensitivity to sounds)

VIII. Vestibulo-cochlear nerve: Deafness, tinnitus (cochlear), dizziness and/or vertigo (vestibular)

IX. Glossopharyngeal nerve: Swallowing difficulty, deviation of soft palate to normal side, anesthesia of posterior pharynx and/or glossopharyngeal neuralgia (unilateral stabbing pain in root of tongue and throat, triggered by coughing, sneezing, swallowing, and pressure on ear tragus)

X. Vagus nerve: Soft palate droop, loss of the gag reflex, hoarseness, nasal voice, and/or loss of sensation at external auditory meatus.

XI. Accessory nerve: Weakness and atrophy of sternocleidomastoid muscle and upper part of trapezius muscle.

XII. Hypoglossal nerve: Paralysis of one side of tongue with deviation to the affected side

Exclusions:

• Skull fracture
• Tumor: meningioma, carcinomatous meningitis, aneurysm
• Infection: herpes zoster, neuroborreliosis, syphilis, mucormycosis
• Miller Fisher syndrome

Associations:

• Nutritional: thiamine deficiency
• Metabolic: diabetes mellitus
• Inflammatory: multiple sclerosis
• Ischemic: giant cell arteritis, brainstem stroke
• Infiltrative: sarcoid

Ascertainment:

History and physical examination

Record:

• Basic descriptors

Anxiety Disorder

Anticipation of danger or misfortune accompanied by apprehension, dysphoria, or tension. Includes generalized anxiety, panic disorder, panic attacks, and obsessive-compulsive disorders.

NB: In most SLE patients, anxiety is a secondary stress reaction and not a direct manifestation of NPSLE.

Diagnostic criteria:

Both of the following:

A. Prominent anxiety, panic disorder, panic attacks, or obsessions or compulsions.

B Disturbance causes clinically significant distress or impaired social, occupational, or other important functioning.

Exclusions:

• Adjustment disorder with anxiety (e.g., maladaptive response to stress of having SLE
• Substance- or drug-induced anxiety
• Anxiety occurring exclusively during the course of an acute confusional state, a mood disorder, or psychosis

Associations:

• Metabolic disorders; e.g., hyperthyroidism, pheochromocytoma
• Marked psychosocial stress
• Corticosteroid use

Ascertainment:

• Standardized instruments, e.g., Hospital Anxiety and Depression Scale when indicated
• History from patients and/or others

Record:

• Basic descriptors
• Type of anxiety

Aseptic Meningitis

Syndrome of fever, headache, and meningeal irritation with CSF pleocytosis, and negative CSF cultures.

Diagnostic criteria:

All the following:

1. Acute or subacute onset of headache with photophobia, neck stiffness, and fever
2. Signs of meningeal irritation
3. Abnormal CSF

Exclusions:

CNS or meningeal inflammation due to:

1. Infection by bacteria, mycobacteria, viruses, fungi, parasites
2. Subarachnoid hemorrhage
3. Malignancy (leukemia, lymphoma, or carcinoma) or granulomatous disease (sarcoidosis)
4. Medications: NSAIDs, intravenous immunoglobulin, azathioprine, etc.

Ascertainment:

History and physical examination

CSF examination for cells, glucose, protein, culture

Record:

• Basic descriptors

Mononeuropathy (single/multiplex)

Disturbed function of one or more peripheral nerve(s) resulting in weakness/paralysis or sensory dysfunction due to either conduction block in motor nerve fibers or axonal loss.

Conduction block is related to demyelination with preservation of axon continuity. Remyelination may be rapid and complete. If axonal interruption takes place, axonal degeneration occurs below the site of interruption and recovery is often slow and incomplete. Sensory symptoms and sensory loss may affect all modalities or be restricted to certain forms of sensation.

Diagnostic criteria:

1. Clinical demonstration of motor/sensory disturbances in the distribution of a peripheral nerve and/or
2. Abnormalities on nerve conduction studies or EMG (i.e., concentric needle examination)

Associations:

• Diabetic neuropathy
• Local damage from mechanical injury, radiation, malignancy, sarcoid
• Infection: Lyme, HIV, herpes
• Vasculitis; polyarteritis nodosa, Wegener’s granulomatosis, cryoglobulinemia, rheumatoid arthritis, Sjögren’s syndrome, etc.

Ascertainment:

History and examination (including nerve conduction studies)

Record:

• Basic descriptors with the following modifications:
• Onset (acute or insidious)
• Description of neurologic deficit
• Course (acute: hours to days/subacute: weeks/chronic: months to years)

Plexopathy

Disorder of brachial or lumbosacral plexus producing muscle weakness, sensory deficit, and/or reflex change not corresponding to the territory of single root or nerve.

Diagnostic criteria:

All of the following:

A. Characteristic signs and symptoms

1. Brachial plexus: deep pain in shoulder, muscle weakness, sensory deficit and/or reflex impairment of arm
   or
2. Lumbosacral plexus: deep boring pain in thigh, muscle weakness, sensory deficit and/or reflex impairment of leg

B. Positive EMG finding (concentric needle examination) and/or nerve conduction studies

for EMG: >1 root or nerve abnormalities with sparing of paraspinal muscles

for NCS: absent or reduced amplitude on motor or sensory nerve conduction

C. Normal MRI or CT scan (optional: myelogram) to rule out a higher neurologic lesion

Exclusions:

• Damage from injury, compression, tumor, aneurysm, radiation
• Cervical rib, thoracic outlet syndrome
• Plexus neuritis
• Toxic: heroin
• Infectious: Lyme disease, leprosy, herpes zoster

Associations:

• Diabetes mellitus
• Polyarteritis nodosa or other vasculitis
• Sarcoid

Ascertainment:

• History and physical examination
• EMG, NCS
• MRI or CT scan (optional: myelogram)

Record:

• Basic descriptors
• Location (brachial vs. lumbosacral)

Cognitive Dysfunction

Significant deficits in any or all of the following cognitive functions: simple or complex attention, reasoning, executive skills (e.g., planning, organizing, sequencing), memory (e.g., learning, recall), visual-spatial processing, language (e.g., verbal fluency), and psychomotor speed. Cognitive dysfunction implies a decline from a higher level of functioning and ranges from mild impairment to severe dementia. It may or may not impede social, educational, or occupational functioning, depending on the function(s) impaired and the severity of impairment. Subjective complaints of cognitive dysfunction are common and may not be objectively verifiable. Neuropsychological testing should be done in suspected cognitive dysfunction, and its interpretation should be done with a neuropsychologist.

Diagnostic criteria:

A. Documented impairment in one or more of the following cognitive domains:

1. Simple attention
2. Complex attention
3. Memory (e.g., learning and recall)
4. Visual-spatial processing
5. Language (e.g., verbal fluency)
6. Reasoning/problem solving
7. Psychomotor speed
8. Executive functions (e.g., planning, organizing, and sequencing)

B. The cognitive deficits represent a significant decline from a former level of functioning (if known).

C. The cognitive deficits may cause varying degrees of impairment in social, educational, or occupational functioning, depending on the function(s) impaired and the degree of impairment.

Associations:

• Substance abuse
• Medication (steroids, sedatives)
• History of learning disabilities
• History of head injury
• Other primary neurologic and psychiatric disorders
• Metabolic disturbances, particularly uremia and diabetes
• Antiphospholipid antibody syndrome
• Coexisting emotional distress, fatigue, and pain.

Ascertainment:

A. Standardized neuropsychological tests to evaluate cognitive domains (79,80) include*:

• Simple Attention: Ability to register and maintain information. Suggested tests include Digit Span (Forward), Continuous Performance Test.
• Complex Attention/Executive Functions: Ability to manipulate information and switch mental set. Examples of tests: Trail Making Test (Part B), Digit Span (Backward), Paced Auditory Serial Addition Test, WAIS III Letter-Number-Sequencing, Stroop Color-Word Test (interference), Wisconsin Card Sorting Test, Category Test.
• Memory: Ability to register, recall, and recognize information. Tested by presenting verbal and nonverbal stimuli which have to be reproduced immediately and after a delay and recognized in the context of other stimuli. Examples of tests: California Verbal Learning Test, Rey Auditory-Verbal Learning Test, Wechsler Memory Scale, Rey-Osterrieth Complex Figure Test Recall, Continuous Visual Memory Test
• Visual-Spatial Processing: Ability to analyze, synthesize, and manipulate visual-spatial information. Tested by presenting visual patterns to be copied, reconstructed, reorganized, or reoriented. Examples of tests: Rey-Osterrieth Complex Figure Test Copy, WAIS-R/III Block Design, Judgment of Line Orientation, Facial Recognition Test, Hooper Visual Organization Test.
• Language: Ability to comprehend, repeat, and produce oral and written material. Examples of tests: Controlled Oral Word Association Test, Thurstone Word Fluency Test, Animal Naming Test, Boston Naming Test, Boston Diagnostic Aphasia Examination (select subtests), Token Test.
• Reasoning/Problem Solving: Ability to reason and abstract. Tests include: WAIS-R/III Comprehension, WAIS-R/III Similarities, Raven’s Progressive Matrices, WAIS-III Matrix Reasoning.
• Psychomotor Speed: Test the ability to rapidly process and produce oral and written information. Appropriate tests include Trail Making Test (Part A), WAIS-R/III Digit Symbol Substitution Test, Stroop Color-Word Test (word-reading and color-naming speed), Simple Reaction Time.
• Motor Function: Manual speed, dexterity, and strength. Tests include Finger Tapping, Grooved Pegboard, Grip Strength.

B. Estimate premorbid level of functioning using currently accepted methods, e.g., demographic data and/or scores on a vocabulary or word-reading test and/or best performance method. A significant discrepancy from premorbid estimate necessary to identify cognitive impairment.

C. Determine impact of cognitive dysfunction on social, educational and/or occupational functioning through interview with patients and significant others and standardized quality-of life-questionnaires such as the SF-36 (37).

Record:

• Basic descriptors with these modifications:
• Type of cognitive dysfunction: Describe areas of deficit.
• Severity: Mild, moderate, and severe dysfunction to be defined by the range of deficits, extent or degree of decline, and impact on everyday functioning. Severe cognitive dysfunction may be limited to a profound disturbance in a single cognitive domain, or it may involve multiple cognitive deficits that include memory and at least one other cognitive domain ("dementia"). Severe and moderate cognitive dysfunction include impairment in everyday functioning. Mild dysfunction may exist in the absence of significant impairment in everyday functioning.
• Duration: Period of time during which current cognitive problems exist as reported by self or by formal testing.
• Objective vs. Subjective Data: Patient reports of cognitive dysfunction should be categorized as "subjective - not tested" or "subjective - tested and not verified."

Autonomic Disorder

Disorder of the autonomic nervous system with orthostatic hypotension, sphincteric erectile/ejaculatory dysfunction, anhidrosis, heat intolerance, constipation.

Diagnostic criteria:

Symptoms and abnormal response to provocative tests:

Test Normal range

• Blood pressure response to standing Fall in BP £ 30/15 mm Hg
  or vertical tilt (systolic/diastolic)
• Heart rate response to standing Increase 11-29 beats/minute
• Heart rate variation with respiration Max. - min. heart rate
  ³15 beats/min.; E:I ratio ³1.2
• Valsalva ratio³ 1.4
• Sweat test Sweating over all body and limbs

E:I ratio = ratio of heart rate during expiration and inspiration

Exclusions:

• Autonomic dysfunction with Lambert-Eaton syndrome
• Medications: tricyclic antidepressants
• Poisons: organophosphates
• Shy-Drager syndrome

Associations:

• Diabetic neuropathy and peripheral neuropathy of other causes
• Autonomic failure in elderly

Ascertainment:

History, physical examination, and provocative tests

Record:

• Basic descriptors
• Type of disturbance

Movement Disorder (Chorea)

Chorea: Irregular, involuntary and jerky movements, that may involve any portion of the body in random sequence. Each movement is brief and unpredictable.

Diagnostic criteria:

Both of the following:

1. Observed abnormal movements
2. Random, unpredictable sequence of movements

Exclusions:

• Wilson’s disease
• Huntington’s disease (and other hereditary disorders)
• Medications (neuroleptics, oral contraceptives, phenytoin, L-dopa, calcium channel blockers)
• Illicit drugs

Associations:

• Stroke, vascular malformation, hypoxic damage
• Tumor
• Pregnancy (chorea gravidarum)
• Rheumatic fever (Sydenham’s chorea)
• Antiphospholipid antibodies

Ascertainment:

• History and examination
• Antiphospholipid antibodies
• Serum copper, ceruloplasmin, slit lamp examination to exclude Wilson’s disease when clinically indicated
• MRI of the brain when clinically indicated

Record:

• Basic descriptors
• Description of abnormal movement

Polyneuropathy

Acute or chronic disorder of sensory and motor peripheral nerves with variable tempo characterized by symmetry of symptoms and physical findings in a distal distribution.

Diagnostic criteria

One or both of the following:

A. Clinical manifestations

1. Clinical demonstration of distal sensory and/or motor deficit
2. Symmetry of signs/symptoms, and/or

B. Confirmation by EMG

1. Concentric needle examination demonstrating denervation of muscle, or
2. Nerve conduction study demonstrating axonal or demyelinating neuropathy

Exclusions:

• Vitamin deficiencies: B₁₂, niacin, thiamine
• Hypothyroidism

Associations:

• Heavy metal and solvent exposures: arsenic, lead, mercury, n-hexane, etc.
• Drug toxicity: isoniazid, vincristine, phenytoin, colchicine, etc.
• Leprosy, HIV, diphtheria, Lyme disease
• Diabetes, uremia, amyloid, alcoholism, porphyria, etc.
• Paraproteinemia, cryoglobulinemia
• Sjö gren’s syndrome
• Inherited forms: Charcot-Marie-Tooth, Fabry’s disease, Tangier’s disease, familial amyloid polyneuropathy, etc.

Ascertainment:

By history and examination and/or electrophysiologic studies

Record:

• Basic descriptors
• Predominant clinical feature (pure motor, pure sensory, motor-sensory or sensory-motor)

Mood Disorders

Prominent and persistent disturbance in mood characterized by

• depressed mood or markedly diminished interest or pleasure in almost all activities OR;
• elevated, expansive or irritable mood

Diagnostic criteria:

I. Major depressive-like episode

One or more major depressive episodes with at least five of the following symptoms, including either A or B or both, during a 2-week period and nearly every day:

A. Depressed mood most of the day, by subjective report or observation made by others

B. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, by subjective report or observation made by others

C.

1. Significant weight loss without dieting or weight gain (>5% of body weight in one month)
2. Insomnia or hypersomnia. Psychomotor agitation or retardation (observable by others, not merely subjective feeling of restlessness or being slowed down)
3. Fatigue or loss of energy
4. Feelings of worthlessness or excessive or inappropriate guilt (may be delusional)
5. Diminished ability to think or concentrate, or indecisiveness
6. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

II. Mood disorder with depressive features
All of the following:

A. Prominent and persistent mood disturbance characterized by predominantly depressed mood or markedly diminished interest or pleasure in all, or almost all, activities

B. Full criteria for major depressive-like episode are not met

III. Mood disorder with manic features
Prominent and persistent mood disturbance characterized by predominantly elevated, expansive, or irritable mood

IV. Mood disorder with mixed features
Prominent and persistent mood disturbance characterized by symptoms of both depression and mania; neither predominates

For all mood disorders:
Symptoms must cause significant distress or impairment in social, occupational, or other important areas of functioning.

Exclusions:

• Primary mental disorders
• Substance-induced mood disorder
• Adjustment disorder with depressed mood

NB: If mood disturbance occurs exclusively during an acute confusional state: classify as acute confusional state if mood disturbance occurs exclusively during a psychotic disorder: classify as psychosis

Associations:

• Marked psychosocial stress
• Corticosteroids

Ascertainment:

• History
• Standardized instruments (e.g., Center for Epidemiological Studies-Depression Scale [CES-D] [33], Hospital Anxiety and Depression Scale [35]) when indicated

Record:

• Basic descriptors
• Type of mood disturbance

Cerebrovascular Disease

Neurologic deficits due to arterial insufficiency or occlusion, venous occlusive disease, or hemorrhage. These are mainly focal deficits but may be multifocal in recurrent disease.

Diagnostic criteria:

One of the following and supporting radioimaging study:

1. Stroke syndrome: acute focal neurologic deficit persisting more than 24 hours (or lasting less than 24 hours with CT or MRI abnormality consistent with physical findings/symptoms
2. Transient ischemic attack: acute, focal neurologic deficit with clinical resolution within 24 hours (without corresponding lesion on CT or MRI)
3. Chronic multifocal disease: recurrent or progressive neurologic deterioration attributable to cerebrovascular disease
4. Subarachnoid and intracranial hemorrhage: bleeding documented by CSF findings MRI/CT
5. Sinus thrombosis: Acute, focal neurologic deficit in the presence of increased intracranial pressure

NB: The finding of unidentified bright objects on MRI without clinical manifestations is not classified at the present time.

Exclusions:

• Infection with space occupying lesions in the brain
• Intracranial tumor
• Trauma
• Vascular malformation
• Hypoglycemia

Associations:

• Diabetes mellitus
• Dyslipidemia
• Atherosclerotic vascular disease
• Atrial fibrillation
• Valvular heart disease
• Atrial septal defect
• Hypercoagulability state
• Antiphospholipid antibody syndrome
• Hypertension
• Smoking
• Cocaine or amphetamine abuse

Ascertainment:

• History and physical examination
• CT or MRI
• Angiogram as indicated
• Antiphospholipid antibodies
• Lumbar puncture as indicated
• EKG for suspected cardiac arrhythmias
• Echocardiography for suspected Libman-Sacks, valvular disease, or atrial septal defect
• Duplex ultrasound of carotid arteries for suspected carotid artery disease

Record:

• Basic descriptors
• Type of cerebrovascular pathology (infarct, hemorrhage, etc.)
• Antiphospholipid antibodies
• Other coagulation studies obtained

Myasthenia Gravis

Neuromuscular transmission disorder characterized by fluctuating weakness and fatigability of bulbar and other voluntary muscles without loss of reflexes or impairment of sensation or other neurologic function.

Myasthenia gravis is an autoimmune disorder mediated by antibodies to acetylcholine receptors. It may occur with other diseases of immunologic origin.

Diagnostic criteria:

A. Characteristic signs and symptoms

One or more of the following:

1. Diplopia, ptosis, dysarthria, weakness in chewing, difficulty in swallowing, muscle weakness with preserved deep tendon reflexes, and, less commonly, weakness of neck extension and flexion, and weakness of trunk muscles
2. Increased weakness during exercise and repetitive use with at least partially restored strength after periods of rest
3. Dramatic improvement in strength following administration of anticholinesterase drug (edrophonium and neostigmine);

and one or more of the following:

B. EMG and repetitive stimulation of a peripheral nerve: In myasthenia gravis repetitive stimulation at a rate of 2 per second shows characteristic decremental response which is reversed by edrophonium or neostigmine. Single fiber studies show increased jitter.

C. Antibodies to Acetylcholine Receptors

Exclusions:

• Congenital myasthenic syndrome, progressive restricted myopathies, steroid and inflammatory myopathies, motor neuron disease
• Multiple sclerosis, variants of Guillain-Barré syndrome (e.g., Miller-Fisher syndrome)
• Organophosphate toxicity, botulism, black widow spider venom
• Eaton-Lambert syndrome
• Stroke
• Medications: neuromuscular blocking agents, aminoglycosides, penicillamine, antimalarial drugs, colistin, streptomycin, polymyxin B, tetracycline
• Hypokalemia; hypophosphatemia

Associations:

• Pure red cell aplasia
• Thyroid abnormalities
• Thymoma

Ascertainment:

• History and physical examination
• Tensilon or neostigmine test (with precautions against respiratory/cardiac complications)
• Anti-acetylcholine receptor antibodies
• 2 Hertz repetitive nerve stimulation (single nerve fiber EMG with jitter studies may be needed)
• Chest CT for thymoma in confirmed myasthenia cases

Record:

• Basic descriptors with the following modification:
• Severity: (Osserman classification) (19):
  I: Ocular myasthenia
  IIA: Mild generalized myasthenia with slow progression: no crises, responsive to drugs
  IIB. : Moderately severe generalized myasthenia : severe skeletal and bulbar involvement but no crises; drug response less than satisfactory
  III: Acute fulminating myasthenia, rapid progression of severe symptoms, with respiratory crises and poor drug response
  IV: Late severe myasthenia, same as III but progression over 2 years from class I to II

Seizures and Seizure Disorders

Abnormal paroxysmal neuronal discharge in the brain causing abnormal function. Isolated seizures are distinguished from the diagnosis of epilepsy. Epilepsy is a chronic disorder characterized by an abnormal tendency for recurrent, unprovoked seizures that are usually stereotypic. Approximately 3% of the population has epilepsy. Typically, provoked seizures result from treatable conditions such as sleep deprivation, toxic exposure to stimulants, withdrawal from narcotics, barbiturates, or alcohol, fever, infection, metabolic disturbances, or SLE.

The approach to the evaluation of patients with a new-onset spell that may be a seizure, and the classification of seizures regardless of whether they are isolated seizures or part of a seizure disorder (e.g., epilepsy), are the same. The approach to treatment, however, is usually different. Although anticonvulsants are effective in controlling seizures acutely whether provoked or not, continuous prophylaxis is principally reserved for patients with epilepsy.

Seizures may occur with or without the loss of consciousness. Seizures are divided into partial and generalized. Partial seizures have clinical or electroencephalographic evidence of a focal onset; the abnormal discharge usually arises in a portion of one hemisphere and may spread to the rest of the brain during a seizure. Primary generalized seizures have no interictal evidence on EEG of focal onset. A generalized seizure can be primary or secondary.

1. Primary generalized seizures (bilaterally symmetric and without local onset)

1. Tonic clonic (grand mal) or tonic or clonic
2. Atonic or astatic seizures
3. Absence seizures (petit mal)
   Typical absences consist of abrupt onset and cessation of impairment of consciousness, with or without automatism, myoclonic jerks, tonic or autonomic components. A 3 Hz spike and wave discharge is usual EEG abnormality. Atypical absences have less abrupt onset and/or cessation of impaired consciousness and are more prolonged in tone with EEG abnormalities other than 3 Hz spike and wave discharge.
4. Myoclonic seizures

2. Partial or focal seizures (seizures beginning locally) (also referred to as Jacksonian, temporal lobe, or psychomotor seizure, according to type)

1. Simple, without impairment of consciousness. Depending upon anatomic site of origin of seizure discharge, initial symptom may be motor, sensory, aphasic, cognitive, affective, dysmnesic, illusional, olfactory, or psychological.
2. Complex, with partial impairment of consciousness, which may be simple at onset, followed by alteration or impairment of consciousness. Symptoms as in 2a.
3. Simple or complex may evolve to secondary generalized tonic/clonic seizures. Sometimes secondary generalization is so rapid that there is no clinical evidence of partial onset, only electroencephalographic.

Diagnostic criteria:

A Independent description by a reliable witness

B EEG abnormalities

NB: EEG is a sensitive tool for diagnosis of epilepsy, but must be used with clinical data. Many epileptic patients have normal interictal EEG. Occasionally, using standard scalp leads, EEG may be normal during a partial simple seizure whereas during complex partial seizures subtle changes are almost always present. Approximately 2-3% of healthy individuals show paroxysmal EEG abnormalities.

Exclusions:

Seizure-like signs or symptoms or seizure from

• Vasovagal syncope
• Cardiac syncope
• Hysteria
• Hyperventilation
• Tics
• Narcolepsy and cataplexy
• Labyrinthitis
• Alcohol and drug withdrawal
• Medications: quinolones, imipenem
• Subarachnoid hemorrhage
• Trauma
• Hypoglycemia
• Panic attacks, conversion disorders, and malingering

Associations:

• Thrombotic-thrombocytopenic purpura/microangiopathy
• Stroke or transient ischemic attack
• Migraine
• Metabolic: hypoglycemia, hypoxemia, uremia
• Tumor
• Infection

Ascertainment:

• History from patient and description from reliable witness
• EEG (specialized studies if necessary)
• Cranial MRI or CT
• Response to anti-epileptic drugs

Record:

• Basic descriptors and,
• Type of seizure (generalized: tonic, clonic, grand mal or absence; partial: simple, complex, or secondarily generalized)
• Frequency/month
• EEG or specialized EEG findings
• MRI or CT result

Psychosis

Definition:

Severe disturbance in the perception of reality characterized by delusions and/or hallucinations

Diagnostic criteria:

All of the following:

A. At least one of the following

1. Delusions
2. Hallucinations without insight

B. The disturbance causes clinical distress or impairment in social, occupational, or other relevant areas of functioning.

C. The disturbance does not occur exclusively during the course of a delirium.

D. The disturbance is not better accounted for by another mental disorder (e.g., mania).

Exclusions:

• Primary psychotic disorder unrelated to SLE (e.g., schizophrenia)
• Substance- or drug-induced psychotic disorder (including NSAIDs, antimalarials)
• Psychologically mediated reaction to SLE (brief reactive psychosis with major stressor)

Associations:

• Marked psychosocial stress
• Corticosteroids

Ascertainment:

History (from patient and others)

Record:

• Basic descriptors
• Type (hallucinations, delusions)

Demyelinating Syndrome

Acute or relapsing demyelinating encephalomyelitis with evidence of discrete neurologic lesions distributed in place and time.

Diagnostic criteria:

Two or more of the following, each occurring at different times,

or one of the following occurring on at least two different occasions

1. Multiple discrete areas of damage to white matter within central nervous system, causing 1 or more limbs to become weak with sensory loss
2. Transverse myelopathy*
3. Optic neuropathy*
4. Diplopia due to isolated nerve palsies or internuclear ophthalmoplegia
5. Brain stem disease with vertigo, vomiting, ataxia, dysarthria, or dysphagia
6. Other cranial nerve palsies*

Exclusions:

• Infections, e.g., TB, HTLV-I, HIV, CMV, Borrelia, CNS Whipple’s disease, progressive multifocal leukoencephalopathy, syphilis
• Vitamin B₁₂ deficiency

Associations:

• Structural lesions, e.g., tumor, arteriovenous malformation
• Familial disorders, e.g., hereditary spastic paraplegia, ataxia, and leukodystrophies
• Sarcoid, Behçet’s disease, other vasculitis
• Multiple sclerosis

Ascertainment:

• History and physical examination
• CSF examination: cell count, protein, oligoclonal bands, IgG index, culture, cytology
• MRI
• Evoked potentials (optional)

Record:

• Basic descriptors

*These are also listed as separate case definitions as they can occur as isolated entities. Patients who meet criteria for these and for demyelinating syndrome should be classified as having both.

Myelopathy

Disorder of the spinal cord characterized by rapidly evolving paraparesis and/or sensory loss, with a demonstrable motor and/or sensory cord level (may be transverse) and/or sphincter involvement.

Diagnostic criteria:

Usually rapid onset (hours or days) of one or more of the following

1. Bilateral weakness of legs with or without arms (paraplegia/quadriplegia); may be asymmetric
2. Sensory impairment with cord level similar to that of motor weakness;
   with or without bowel and bladder dysfunction.

Exclusions:

• Mass lesion causing compression of or within spinal cord (e.g., prolapsed disc, tumor, hematoma, or ruptured spinal arteriovenous malformation).
• Cauda equina lesion

Associations:

• Preexisting demyelinating syndrome
• Infections: herpes zoster, HIV
• Antiphospholipid antibodies

Ascertainment:

• History and physical examination:
• MRI or CT, myelogram as emergency
• CSF examination: cell count, protein, culture , oligoclonal bands, IgG index, cytology

Record:

• Basic descriptors
• Clinical features
• MRI/CT findings

Acute Confusional State

Disturbance of consciousness or level of arousal characterized by reduced ability to focus, maintain, or shift attention, and accompanied by disturbances of cognition, mood, affect, and/or behavior. The disturbances typically develop over hours to days and tend to fluctuate during the course of the day. They include hypo- and hyperaroused states and encompass the spectrum from delirium to coma.

NB: "Acute Confusional State" is equivalent to "delirium" defined in DSM-IV and ICD-9 as an observable state of impaired consciousness, cognition (including perception), mood, affect, and behavior. The definitions of delirium in DSM-III, DSM-III-R, and DSM-IV have been tested for reliability, and the committee wanted a definition that would conform to ICD-9, WHO, and DSM-IV.

Neurologists often use "encephalopathy" where psychiatrists use "delirium" to describe the same clinical state. Encephalopathy is defined in neurologic texts as a diffuse cerebral dysfunction associated with a disturbance in consciousness, cognition, and mood, affect, and behavior. It implies a physiologic etiology and is usually used with descriptors of various metabolic disorders.

"Organic brain syndrome" is not recommended for usage since there is better studied terminology.

Acute confusional states are generally accompanied by cognitive deficits. If cognitive deficits are the only CNS manifestations, the illness should be recorded as "Cognitive Dysfunction."

Diagnostic criteria:

Disturbance of consciousness or level of arousal with reduced ability to focus, maintain, or shift attention, and one or more of the following developing over a short period of time (hours to days) and tending to fluctuate during the course of the day:

A. Acute or subacute change in cognition that may include memory deficit and disorientation.

B. A change in behavior, mood, or affect (e.g., restlessness, overactivity, reversal of the sleep/wakefulness cycle, irritability, apathy, anxiety, mood lability, etc.)

Exclusions:

• Primary mental/neurologic disorder not related to SLE.
• Metabolic disturbances (including glucose, electrolytes, fluid, osmolarity)
• Substance or drug-induced delirium (including withdrawal)
• Cerebral infections

NB: Preexisting cognitive deficits are not an exclusion. If acute confusional state is superimposed on preexisting cognitive deficits, diagnose both.

Associations:

• Marked psychosocial stress
• Corticosteroid use
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

Ascertainment:

Disturbed consciousness: Clinical observation, mental status, and neurologic examination.

Cognitive function: Mental status examination, including instruments such as the Mini Mental Status Examination (32). For more detailed assessment, see Cognitive Dysfunction category.

Mood and behavioral dysfunction: Clinical observation, history by patient and others, standardized instruments (e.g., Hospital Anxiety and Depression Scale) (35).

Determine from the individual or from informants the impact of disturbance on daily life, previous occupational and social functioning.

Record:

• Basic descriptors