What are the specific diagnostic criteria used for various neurology diseases?

Diagnostic Criteria for Common Neurological Diseases

Multiple Sclerosis (MS)

The diagnosis of multiple sclerosis requires evidence of CNS lesions disseminated in both space and time, with no better explanation for the clinical presentation, following the McDonald criteria. 1

Core Diagnostic Requirements:

• Dissemination in Space (DIS): At least 3 of the following:

  • ≥1 periventricular lesions
  • ≥1 juxtacortical lesions
  • ≥1 infratentorial lesions
  • ≥1 spinal cord lesions 1, 2

• Dissemination in Time (DIT): Demonstrated by either:

  • New T2 or gadolinium-enhancing lesion on follow-up MRI
  • Simultaneous presence of gadolinium-enhancing and non-enhancing lesions 1, 2

Clinical Presentation Requirements:

Clinical Presentation	Additional Data Needed for MS Diagnosis
Two or more attacks; objective clinical evidence of 2+ lesions	No additional tests required
Two or more attacks; objective clinical evidence of 1 lesion	DIS by MRI or 2+ MRI lesions consistent with MS plus positive CSF
One attack; objective clinical evidence of 2+ lesions	DIT by MRI or second clinical attack
One attack; objective clinical evidence of 1 lesion	DIS by MRI or 2+ MRI lesions plus positive CSF AND DIT by MRI or second attack
Insidious neurological progression suggestive of MS	DIS by specific MRI criteria AND DIT by MRI or continued progression for 1 year [1]

Supporting Tests:

• CSF analysis: Oligoclonal bands and raised IgG index
• Visual Evoked Potentials (VEP): Particularly useful when MRI abnormalities are few 2, 1

Guillain-Barré Syndrome (GBS)

Guillain-Barré syndrome is diagnosed based on progressive bilateral weakness of arms and legs with absent or decreased tendon reflexes, typically developing over days to 4 weeks. 2

Required Features:

• Progressive bilateral weakness of arms and legs (initially only legs may be involved)
• Absent or decreased tendon reflexes in affected limbs 2

Strongly Supporting Features:

• Progressive phase lasting from days to 4 weeks (usually <2 weeks)
• Relative symmetry of symptoms and signs
• Mild sensory symptoms and signs
• Cranial nerve involvement, especially bilateral facial palsy
• Autonomic dysfunction
• Muscular or radicular back/limb pain
• Increased CSF protein with normal cell count (albumino-cytological dissociation)
• Electrodiagnostic features of motor or sensorimotor neuropathy 2

Features Casting Doubt on Diagnosis:

• Increased CSF cells (>50×10⁶/l)
• Marked persistent asymmetry of weakness
• Bladder/bowel dysfunction at onset
• Severe respiratory dysfunction with limited limb weakness at onset
• Sharp sensory level
• Hyper-reflexia or extensor plantar responses 2

Autoimmune Encephalitis

Autoimmune encephalitis is diagnosed based on clinical features of encephalopathy plus specific antibody testing, neuroimaging findings, and CSF analysis showing inflammation. 2

Diagnostic Approach:

• Clinical: Subacute onset of working memory deficits, altered mental status, or psychiatric symptoms
• MRI: T2-FLAIR hyperintensities in medial temporal lobes (limbic encephalitis) or specific patterns:
  • Radial perivascular enhancement in autoimmune GFAP astrocytopathy
  • Punctate brainstem/cerebellar enhancement in CLIPPERS 2
• EEG: Focal slowing/seizures, lateralized periodic discharges, extreme delta brush (in NMDAR encephalitis)
• CSF: Inflammatory changes (pleocytosis, elevated protein, oligoclonal bands)
• Brain FDG-PET: May show abnormalities when MRI is negative 2

Anatomical Classification:

Type	Differential Diagnosis	Additional Testing
Limbic encephalitis	HSV, VZV, HHV6	CSF viral PCR, CSF VZV IgG/IgM
Cortical/subcortical	ADEM, tumefactive MS, CJD	MOG-IgG, CSF JCV PCR, CSF prion panel
Striatal encephalitis	CJD, WNV, toxic encephalopathy	Prion panel, WNV IgM, toxicology screen
Brainstem encephalitis	Listeria, viral, CLIPPERS	CSF bacterial culture, viral PCR [2]

Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt-Jakob disease diagnosis requires rapidly progressive dementia plus specific biomarkers including RT-QuIC, 14-3-3 proteins, characteristic MRI findings, or typical EEG patterns. 2

Diagnostic Criteria:

• Clinical: Rapidly progressive dementia
• CSF Biomarkers:
  • Positive RT-QuIC (highest specificity)
  • Positive 14-3-3 protein
  • Elevated t-Tau and abnormal p-Tau/t-Tau ratio 2
• MRI: Hyperintensities on DWI/FLAIR in:
  • Caudate nucleus and putamen
  • At least two cortical regions (temporal, parietal, occipital)
• EEG: Periodic sharp wave complexes (PSWCs) 2

Diagnostic Process:

• Complete clinical investigation
• Blood sampling
• Lumbar puncture for CSF analysis
• MRI (DWI and ADC maps most sensitive)
• EEG 2

Parkinson's Disease

Parkinson's disease diagnosis requires the presence of bradykinesia plus either rest tremor or rigidity, along with supportive criteria and absence of exclusion criteria or red flags. 3

Core Features:

• Bradykinesia
• Rest tremor or rigidity 3

Supportive Criteria:

• Clear response to dopaminergic therapy
• Presence of levodopa-induced dyskinesias
• Rest tremor of a limb
• Olfactory loss or cardiac sympathetic denervation 3

Absolute Exclusion Criteria:

• Cerebellar abnormalities
• Downward vertical supranuclear gaze palsy
• Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
• Parkinsonian features restricted to lower limbs for >3 years
• Treatment with dopamine blockers or dopamine-depleting agents
• Absence of response to high-dose levodopa 3

Neuromyelitis Optica Spectrum Disorder (NMOSD)

Neuromyelitis optica diagnosis requires optic neuritis, myelitis, and at least two of three supportive criteria: longitudinally extensive spinal cord lesion, brain MRI non-diagnostic for MS, or NMO-IgG seropositivity. 4

Core Clinical Features:

• Optic neuritis
• Acute myelitis 4

Supportive Criteria (need at least 2):

• MRI evidence of contiguous spinal cord lesion extending ≥3 segments
• Brain MRI not meeting MS diagnostic criteria
• NMO-IgG (aquaporin-4 antibody) seropositivity 4

AQP4-IgG Positive NMOSD:

• Only one core clinical characteristic required
• Core characteristics include:
  • Optic neuritis
  • Acute myelitis
  • Area postrema syndrome
  • Acute brainstem syndrome
  • Symptomatic narcolepsy or acute diencephalic syndrome
  • Symptomatic cerebral syndrome 2

Vascular Dementia

Vascular dementia diagnosis requires both evidence of cognitive impairment and cerebrovascular disease, with a clear temporal relationship between vascular events and cognitive decline. 5

Diagnostic Components:

• Presence of dementia syndrome
• Evidence of cerebrovascular disease (clinical and imaging)
• Relationship between the above two disorders 5

NINDS-AIREN Criteria:

• Cognitive decline in memory and ≥2 other domains
• Cerebrovascular disease by neuroimaging (strategic infarcts or multiple lacunes)
• Temporal relationship between stroke and dementia onset
• Exclusion of other causes 5

Functional Neurologic Disorders

Functional neurologic disorders are diagnosed based on positive clinical features that are inconsistent with organic disease patterns, rather than solely by exclusion of other neurological conditions. 6

Diagnostic Approach:

• Identify positive features inconsistent with organic disease
• Document specific signs (e.g., Hoover's sign, give-way weakness)
• For psychogenic non-epileptic seizures (PNES):
  • Record typical events (ideally with video-EEG)
  • Identify specific semiological features distinguishing from epileptic seizures 6

Key Diagnostic Features:

• Variability and inconsistency of symptoms
• Distractibility
• Suggestibility
• Entrainment of tremor
• Non-anatomical sensory patterns
• Normal neurophysiological studies despite severe symptoms 6

Clinical Pearls

1. Diagnostic Pitfalls: Misdiagnosis often occurs due to misinterpretation of MRI findings, applying criteria to atypical presentations, inadequate CSF analysis, or overlooking "red flags" 1.

2. Biomarker Limitations: All biomarkers have reduced sensitivity in early disease stages and in certain subtypes; follow-up investigations may be necessary when initial results are negative 2.

3. Diagnostic Hierarchy: For most neurological conditions, the diagnostic process follows a pattern of clinical assessment, neuroimaging, and laboratory/electrophysiological confirmation, with relative emphasis varying by condition 7.

4. Differential Diagnosis: Always consider conditions that can mimic the primary suspected diagnosis, particularly when atypical features are present 2, 1.