Differential Diagnosis in Neurology

2.4. Partial Seizures

• Simple motor partial seizure:
  • Motor signs and symptoms depend on the area of the motor cortex activated
  • Motor cortex (patterns of spread of the primary motor cortex):
    • Thumb initiates clonic movements followed by twitching of the corner of the mouth and arm; spread is then to the distal leg, the shoulder is often spared
    • Distal leg to proximal leg. The trunk may be spared. Spread is next to the hand, thumb and face
    • Simple partial motor seizure, particularly of the upper extremity may last for days to weeks
      • Menshikoff's syndrome
      • Usually follows old vascular lesion
      • Very difficult to treat

Simple Sensory Partial Seizures

• Jacksonian march very similar to that noted with motor seizures
• Face and hand particularly involved (low threshold of neurons to fire; large cortical area)
• Trunk is involved in a sensory "march" or spread with simple sensory seizure
• Areas of origin: usually primary homunculus of S1 or posterior parietal sensory area 5 and 7
• Occasionally sensory seizures may begin in proprioceptive components of the sensory cortex with consequent posturing of the affected extremity; may be initiated by a specific posture
• Posterior partial sensory seizures may initiate a feeling of tingling in a parietal sensory distribution. Patients may also feel tired
• SII involvement: causes a sensation of heat that spreads from the feet and envelops the body bilaterally. Most often from spread of a temporal lobe focus

Occipital Lobe Seizures

Seizures emanating from the occipital lobe present a variety of neurological signs and symptoms. In general, forced eye versive movements are a frontal lobe phenomena, but may also occur from seizures of the parietal occipital junction. Oculogyric or oculoclonic eye movements (tonic or clonic contraversive gaze deviation) may occur from occipital seizure foci.

Visual symptoms are the most common symptoms of occipital lobe seizures. BA17 is associated with non-colored flashes of light, teichopsia, scotomata, hemianopia or blindness. BA 18 and BA 19 association area seizures are associated with moving geometric forms that are colored or patterned (photopsia). If the seizure spreads to the temporal-parietal occipital junction complex visual images may be noted. These consist of visual distortions, micropsia, macropsia, perception abnormalities or visual hallucinations. The later usually are images of past experiences that also may be distorted.

Occipital Lobe Visual Simple Partial Seizure

• Occipital pole - BA 17
  • Patients' experience simple non-colored flashes of light (dots or stars or flashes; in general they do not move across the visual field)
• BA 18 and BA 19 visual association cortex:
  • Colored (red, green, yellow, blue) geometric figures are experienced
  • Figures move across the contralateral visual field
• Posterior temporal/parietal/occipital junction:
  • Specific distortions of the visual object occur
  • Images are colored
  • Associated with other temporal lobe semiologic phenomena
• Unilateral eye blinking
• May have cortical blindness
• Epileptic akinetopsia
  • Illusory motion perception
  • Occurs in the contralateral field from the focus
• Epileptic monocular nystagmus

Non-Tumoral Occipital Temporal Epilepsy

• Seizures from occipital lobes demonstrate heterogeneous patterns of spread
  • Spread through inferior longitudinal fasciculus to the temporal lobe
    • This is sufficient spread to activate cortical mediotemporal structures
  • Occipital lobe signs and symptoms:
    • Forced eye blinking
    • Blurred vision
    • Flashing lights
    • Ictal blindness
    • Elementary visual hallucination (rare)
• Signs of occipital seizure spread to temporal lobe:
  • Visual component
  • Psychical aura
  • Olfactory aura
  • Dizziness
  • Somatosensory aura
• Seizures with occipital lobe symptoms:
  • Approximately 2/3 have temporal auras
  • 1/3 have both temporal and frontal auras
• Periventricular subcortical nodular heterotopias present with temporal-parieto-occipital semiology
• Focal cortical dysplasia includes polymicrogyria, heterotopias and abnormal lamination. Migrational disorders tend to occur posteriorly. The causes of these disorders if post migrational are:
  • Watershed MCA/PCA hypoperfusion
  • Prenatal occlusion of the precuneus branch of the PCA (parieto-occipital area)
• Clinical features of bilateral parasagittal and parieto-occipital polymicrogyria induced seizures are:
  • Complex partial seizures with minor automatisms
  • Patients maintain an average IQ or suffer mild mental retardation
• Photo sensitive epilepsy with absence and absence status:
  • Clinical features:
    • Usually children
    • Early or late onset of benign childhood partial seizures with occipital paroxysms
    • Seizures are elicited by elimination of central vision and fixation
    • Seizures persist as long as the eyes are closed
    • Seizure activity inhibited by patterned vision
    • Seizure types:
      • Brief absences
      • GTCS
      • Atypical absence status

Differential Diagnosis between Occipital Seizures versus Migraine Headaches

• Vomiting may be ictal (right temporal lobe) or part of migraine
• Hemicranial headache:
  • Seizure focus is in the amygdala or hippocampal formation (ipsilateral)
  • May also be accompanied by nausea and vomiting (most often migraine)
• Rapid onset and resolution of symptoms are most often an epileptic discharge
• Points favoring migraine:
  • Prolonged attack
  • Severe nausea and vomiting preceded by a visual aura
  • Slight impairment of processing rather than complete unresponsiveness

Photosensitive Epilepsy (PSE)

• Affects 1:4000 seizure patients
• Most prevalent in adolescence
• High incidence of family history of epilepsy in PSE
• General features:
  • Stimuli are flashing lights or high contrast patterned stimuli
  • Chromatic sensitivity
  • Stimulus frequency: 10–30 Hz
  • Pattern sensitivity: 0.5 to 6 cycles/degree
    • Chromatic sensitive seizure variant
    • Photoparoxysmal response to rapid color frame changes (blue to red; monochromatic light)

Epilepsy Provoked by Television and Video Games

• EEG activated by:
  • Video screens
  • Flickering screen light
  • Patterns produced parallel lines that form the image
  • Frequency of 25 Hz activate 75% of patients
  • Seizure types:
    • Absence
    • Myoclonic
    • Tonic clonic
    • Occipital lobe partial
• Sensitivity to seizures increases:
  • Screen brightness
  • Highly contrasted pattern
  • Fatigue
  • Fever
  • Close distance
  • Sleep deprivation

Fixation-Off Sensitive Seizures (FOS)

• Elimination of central vision and fixation induces spikes on EEG
  • Unilateral or bilateral
  • High amplitudes

Division A: Temporal Lobe Epilepsy

The major seizure problem in adults and the source of 75% of intractable epilepsy is complex partial epilepsy of temporal lobe origin. The spectrum of symptoms is wide and the semiology differs from patient to patient. The symptoms reported may be the only ones remembered and not in the area that initiated the seizure.

MRI techniques, PET and SPECT evaluations as well as intraparenchymal recordings now demonstrate significant abnormalities in medial temporal lobe areas and migrational defects that involve the germinal matrix, and focal dysplasia (abnormal lamination) within the cortex itself. Many intractable patients suffer the dual pathology complex of medial hippocampal sclerosis and migrational disorder. Extra temporal foci with spread from the frontal parietal and occipital lobe are a major clinical phenomenon.

Genetics of Temporal Lobe Epilepsy (TLE)

Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF):

• Chromosome 10q: gene LG 1 I (leucine rich glioma inactivated protein)
• Clinical features:
  • Onset in the first to third decades
  • Not preceded by febrile convulsions
  • MRI shows no focal lesions
  • Some patients have a receptive aphasic
  • Some patients have visual symptoms
  • May be developmental abnormality in the affected cortex in 50% of patients
• LG 1 I gene mutations:
  • First described in glial tumors; deletions or rearrangements
  • Cause protein truncation; putative loss of function

Familial Mesial Temporal Lobe Epilepsy (FMTLE)

• Clinical features:
  • Onset in the second to fifth decade
  • No MRI lesions in the temporal lobe or hippocampal formation
  • No prior febrile convulsions
  • Autonomic and psychic auras; high incidence of déjß vu as an aura

FMTLE Associated with Hippocampal Sclerosis:

• Genetics:
  • Some families AD inheritance
• Hippocampal sclerosis may be caused by:
  • Prolonged childhood convulsion
  • Encephalitis
  • Developmental or migrational defect
  • Putative genetic component

FMTLE Associated with Febrile Convulsions

• Genetics:
  • One French family-digenic inheritance
    • First to second decade of life onset of seizures
    • Benign course
    • No MRI or temporal lobe lesions
  • ADTLE with FS
    • Young age at onset
    • Multiple febrile convulsions
    • No déjß vu, auditory or visual hallucination
    • No hippocampal sclerosis

Febrile seizures with medial Temporal Lobe Epilepsy

• Genetics:
  • Families may have many members with febrile convulsions and a few with TLE
• Clinical features:
  • Association in some patients between prolonged febrile convulsion and HF sclerosis

HIMAL

• Possible familial occurrence
• Incomplete inversion of the hippocampus
• Normal size and hippocampal MRI signal
• Blurred internal structure

Temporal Lobe Epilepsy in the Spectrum of Partial Epilepsy Syndromes

• Clinical features:
  • Familial partial epilepsies: TLE is part of the seizure spectrum

• Specific Syndromes:
  • Familial partial epilepsy with variable foci (FPEVF)
    • Onset first to third decade
    • Heterogeneous seizure types
    • No associated MRI defects or febrile convulsions
  • Genetics of FPEVF
    • Possible linkage to 2q
    • Two large Canadian families linkage to 22q 11–q12
• Partial epilepsy with pericentral spikes (PEPS)
  • Clinical features:
    • Benign
    • Onset first to second decade
    • Brazilian family
    • Pericentral spikes on EEG
    • No MRI or febrile convulsions
  • Genetics:
    • Linkage to 4p 15
• Miscellaneous genes putatively important for TLE:
  • IL1B gene
  • Subunit opioid gene
  • Prodynorphin gene
    • Chromosome 20
  • 8q epilepsy
  • FAME (familial adult myoclonic epilepsy)
  • BAFME (Baltic familial myoclonic epilepsy)
  • FCT (familial cortical tremor)
  • Epileptic monocular nystagmus

General features of Temporal Lobe Epilepsy

• May begin at infancy or in old age; most patients have their first seizure in late childhood or early adulthood
• 75% of patients experience auras of simple partial seizures originating in the temporal lobe
• Genetic forms:
  • Familial
  • Chromosome localization as noted above
• Risk factors for TLE
  • Head trauma
  • Difficult birth (prolonged delivery, forceps, obstetric complications)
  • Genetics
  • Family history
  • Neuronal migration defects
• Auras are experienced either independently or as the first phase of a complex partial seizure
• 50% of patients have unilateral or bilateral secondary generalized tonic; clonic or tonic-clonic seizures
• Secondary generalization may cause a tonic drop attack; greater than 80% of GTCS are secondarily generalized from TLE

Clinical features of Temporal Lobe Epilepsy

• Prodrome; an awareness of an impending seizure days in advance. Prodromes consist of:
  • Headache
  • Irritability
  • Insomnia
  • Personality change
  • Depression
• Complex partial seizures are either:
  • Initiated by an aura
  • Start with impairment of consciousness

Auras

An aura: That portion of the CPS that occurs before consciousness is lost (if it is) and is remembered. The aura is an ictal event.

General Features of Automatisms:

• Involuntary motor activity occurring during the period of impaired consciousness
• Patient is partially or totally amnestic for the behavior
• May continue or begin in the post ictal period
• May be a continuation of movements that occurred prior to the seizure (perservative) or may be a new (de novo) movement
• Motor activity is usually fragmentary; rarely are these sequential coordinated movements
• Automatisms vary from patient to patient, but are stereotyped for an individual patient
• May occur with absence seizures and in the post ictal phase of a generalized tonic-clonic seizure
• HF-amygdala complex; rarely meso orbital frontal lobe and ungulate gyrus are the initial site of origin of motor automatisms. Oral buccal automatisms most often originate from the amygdala frontal operculum.

Patterns of Clinical Automatisms

• Oro-buccal lingual: smacking of the lips, chewing, swallowing, choking, eating, spitting abnormal tongue movements and water drinking (amygdala; frontal operculum)
• Gestural: repetitive movements of the hands and fingers; may be semi purposeful (drawing, playing cards) rubbing the nose (ipsilateral focus)
• Sexual: masturbation, pelvic thrusting
• Expressional: facial expressions of fear anxiety, confusion or anger
• Motor: walking (poriomania), running (cursive); circling with arms raised
• Speech: crying (dachrymistic), laughing (gelastic); repeating phrases; screaming

The Sequence of Motor Automatisms

• Arrest phenomena:
  • Patient stops activity and maintains a posture for a few seconds
• Autonomic phenomena
  • Loss of facial expression associated with pallor
• Onset of motor phenomena
  • Motor automatisms originate most often in the amygdala and amygdala fugal pathways as well as pre-motor and supplementary motor cortex patterns from temporal lobe and frontal lobe

Psychic symptoms:

• Often preceded by alterations in consciousness
  • Important in localization
  • General rules:
    • Severe anxiety: anterior temporal lobe
    • Complex phenomena (neocortical) lateral temporal lobe
    • Fear, impending doom: medial temporal lobe
• Complex cognitive emotional states (lateral temporal lobe; right side greater than the left)
  • Dream state
  • Detachment and strangeness
  • Autoscopy: feeling as if you are watching the event
  • Time distortion (usually too slow)
  • Feelings of unreality
  • Forced thinking (continued thinking of a specific thought or phrase)
  • Blocking thought
• Affective symptoms
  • Ictal fear; poorly localized, may be associated with abdominal sensation, impending doom, an overwhelming quality (amygdala or medial HF)
  • Sadness (common)
  • Depression (common)
  • Embarrassment (usually medial frontal lobe)
  • Joy (rare)
  • Ecstasy (rare)
  • Crying (dachrymistic): often bilateral temporal lobe foci (mirror focus); may be ictal or post ictal
  • Sexual feelings (orgasm right temporal hemisphere)
  • Altered body sensation
  • Gelastic (laughing): more common with hypothalamic lesions (particularly hamartomas); laughter without mirth, not elaborated correctly; patient may be fearful while laughing
• Distortion of memory:
  • Déja vu: as if the experience had occurred before:
    • déja-vu: visual experience
    • Entendu: auditory experience
    • Jamais-vu: prior experience or place is experienced as new or unfamiliar
    • Vivid "flashbacks" of past events
    • Special sensory symptoms
• General features:
  • Alterations of perception
    • Unusual clearness
    • Heightened sensitivity
    • Premature poorly formed hallucinations (primary visual and auditory receptive areas)
    • Complex hallucinations from association areas
• Fear as a main feature of an epileptic seizure
  • Localization of the primary epileptic zone:
    • Right temporal
    • Bitemporal
    • Frontal
  • Behavior:
    • Sensation of fear
    • Autonomic symptoms
    • Coordinated behavior
  • Neuroanatomical Networks Involved
    • Orbito frontal cortex
    • Anterior cingulate gyrus
    • Temporal limbic system
      • Amygdala to the anterior cingulate gyrus
  • Clinical features of a panic attack (psychiatry):
    • Sudden spontaneous onset (rarely a trigger)
    • Intense fear and discomfort
    • Impending doom thoughts of dread
    • Feelings of being trapped; losing control
    • Last for a few minutes
    • Full recognition and remembrance of the attack
  • Fear as a manifestation of amygdala seizure:
    • Anticipatory anxiety
    • Expression of impending doom
    • Buccal automatism
    • Autonomic disturbance
    • Complex behavioral automatisms
    • Early in the seizure a call for help; anxiety
    • Incomplete recall for the event

Visceral Auras

• Olfactory (uncus of the hippocampal gyrus); uncinate fits
  • Unpleasant smells; burning rubber, garbage, fecal material, acid; rarely pleasant (usually an exaggeration of the pleasant quality)
  • May be produced by stimulation of:
    • Amygdala
    • Olfactory bulb
    • Uncus
    • Posterior orbital frontal cortex
  • Olfactory auras may be associated with:
    • Intellectual aura
    • Gustatory, visual and auditory auras
• Taste (enterorhinal cortex of the temporal lobe)
  • Unpleasant: blood, bitter, chemical, rotting, metallic
  • Rare pleasant (usually a too sweet taste)
• Abdominal aura:
  • General characteristics:
    • Occurs in 20–60% of patients with TLE
    • Approximately 20% of patients with extra temporal epilepsy
    • Approximately 65% with mesial temporal lobe origin on 35% with neocortical origin
    • Occurs in extratemporal locations:
      • 5% perirolandic
      • 17–20% parieto occipital
      • 3% frontal lobe
    • Occurs primarily from posterior insular cortex; frontal orbital areas connect to anterior insular cortex
  • Specific simple sensations:
    • Epigastric rising sensation
    • Feeling of having to defecate
    • "flip flop" of the stomach
    • Automatism follow abdominal auras
  • Associated symptoms with abdominal aura
    • Epigastric aura
      • Ictal vomiting
    • Subjective fear
    • Oro-alimentary symptoms
  • May evolve into clonic seizures
    • Occurs in 2/3 patients with frontal lesions
  • Abdominal pain in TLE
    • Pain occurs in 5% of all abdominal auras
    • Pain occurs in 50% of all abdominal auras that originate from the frontal lobe
    • Painful abdominal auras may originate from parietal areas
• Rare visceral auras:
  • Burning, tingling, gnawing, choking, throat sensations
  • Ictal hunger (right temporal lobe)
  • Ictal thirst (amygdala to hypothalamus)
  • Severe pain or unusual genital sensations
  • Severe vomiting (right temporal focus)
  • Goose bumps
  • Coldness-shivering (left temporal lobe)
  • Expectorations (left temporal lobe)
• Cardiac and chest aura (anterior insular cortex)
  • Heart racing or pounding
  • Pain in the central chest (no cardiac radiations)
  • Cardiac arrhythmias (atrial or ventricular)
• Post ictal coughing and nose rubbing
  • Ictal activation of central autonomic pathways
  • Post ictal coughing
    • Reaction to increased respiratory secretions
  • Postictal coughing > postictal nose rubbing
  • Post Ictal Coughing
    • Earlier in onset than PIN rubbing
    • PIC just prior to ictal off set
    • PIC > temporal lobe than extra temporal focus
    • Right sided mesial temporal lateralization
    • Ipsilateral to moving hand (postictal nose rubbing)

Visual Auras

• Blurred vision
• Micropsia (objects too small)
• Macropsia (objects too large)
• Perceptual illusions: objects too far or too close
• Distorted objects
• Rare: clear visual hallucinations (evergreen tree in temporal field)
• Kinesogenic illusions of movement (medial temporal gyrus)

Auditory Auras

• Sound or voices not clearly perceived
• A1 auditory receiving area aura: clicking, roaring, wind blowing, rumbling sounds
• Receptive aphasia (left sided BA 22 or BA 23)
• Distorted or muffled sounds
• Sounds too loud or too soft
• Extremely rare: auditory hallucination (most often a psychiatric or drug withdrawal phenomenon)
• Macropsia or micropsia

Vestibular Auras

• Non-specific dizziness or light-headedness. One of the most frequent TLE aura's (probable superior temporal area or intraparietal gyrus)
• Tornado seizures: severe vertigo, with patient spinning rapidly and falling to the ground (superior temporal lobe or intraparietal gyrus)

Cephalic Auras

• Head too big or small
• Off of the body
• Ice pick (stabbing) headache (also occurs with migraine)
• Squeezing compression of the head
• Unusual position on the neck

Post Ictal Signs and Symptoms of CPS of Temporal Lobe Origin

• Gradual transition between the seizure and postictal state
• Automatisms may continue during post ictal period
• Deep sleep is unusual
• Severe fatigue that may last for hours ("drained")
• Period of confusion and disorientation following the event (less than one-minute usually, but may last for 30 minutes)
• Moderate dull headache, occasional vomiting or nausea
• Post ictal thirst; (common); hunger is rare
• Postictal hyperhidrosis
• Aimless wandering (poriomania)
• Simple partial seizure from the temporal lobe (dizziness, abdominal sensations, déja vu or jamais vu) last less than 60 seconds and has no postictal symptoms
• Postictal psychosis

Medial Temporal Lobe Localizing Features:

• Uncinate auras (abnormal smells and tastes)
• Impending doom
• Automatisms (licking of lips, chewing, swallowing)
• Arrest response (sudden freezing)
• Searching head movements
• Contralateral dystonia, body shifting
• Cough or sigh
• Amnesia (hippocampal formation)
• Gustatory
  • Nausea
  • Butterflies
  • Borborygmi

Lateral Temporal Lobe Localizing Features:

• Wernicke's aphasia; speech arrest left side
• Psychical auras (right temporal lobe > left)
  • Jamais vu
  • Déjà vu
    • Auditory experiences (entendu)
  • Forced thinking (episodes from past life experience)
  • Dreamy state
  • Heightened sensations
  • Feelings of pleasure or extreme pleasure
  • Depression or euphoria
  • Epileptic rage
  • Detachment
  • Unreality

Anterior Temporal Lobe Cortex

• Panic attacks, anxiety
• No precipitating cause (precedes the event)
• Stereotyped
• Associated with autonomic features:
  • Sweating
  • Hyperventilation
  • Pupillary dilatation

Medial temporal lobe syndrome

• Hippocampal sclerosis:
  • MRI findings:
    • Hippocampal atrophy
    • Increased T2 signal
    • Disrupted internal structure of the hippocampal formation
    • Increased size of ipsilateral temporal horn
    • Focal thickening of the fimbria
  • Dual pathology:
    • Neuronal loss within the hippocampal formation (HF)
    • Extra hippocampal lesion:
      • Migrational defects
      • Scar
      • Tumor
      • Vascular malformation
      • Porencephaly
      • Hamartoma
    • Occurs in approximately 30% of patients with hippocampal sclerosis
    • 16% of hippocampal sclerosis patients have bilateral abnormalities on MRI in the hippocampal formation
    • Loss of cells primarily CA1 and CA3 in the HF
  • Hippocampal sclerosis occurs without hippocampal formation atrophy in 5–10% of patients; normal volume of hippocampal formation
  • Younger children less than 12 years with hippocampal formation atrophy
    • Dysplastic lesions and hamartomas more common than astrocytic tumors
  • Clinical features of hippocampal sclerosis:
    • Early age at onset of seizures
    • Prolonged febrile convulsions important in etiology; seizure free interval after initial febrile convulsion
    • Material specific memory deficit
    • Executive and attention attributes are intact
    • Deficits in:
      • Verbal comprehension
      • Perceptual organization
      • Verbal memory
      • Some visual spatial abilities
      • No generalized cognitive impairment
      • Impairment of access to an array of cognitive functions rather than restricted pattern of memory loss
    • Postictal psychosis common
    • Autonomic auras
    • Automatisms (oro-buccal-pharyngeal)
    • Ictal fear
    • Limbic seizures occur in the late afternoon and early evening
• Amygdala sclerosis:
  • 10% evolve into medial temporal lobe seizures
  • Amygdala and hippocampal formation involvement: 50% origin of ictal events in MTLE
  • Pathology of amygdala sclerosis:
    • Microdysgenesias (microscopic variant of cortical dysphasia)
    • Vascular lesions
    • Cortical dysplasia
    • Abnormal glial cells (large hyperchromatic)
    • Hamartoma (abnormal clusters of neurons and neuroblast cells)
    • Tumor
  • Clinical features:
    • Seizure onset later than that of hippocampal sclerosis
    • Amygdala sclerosis on the same side as hippocampal sclerosis in 50–70% of patients
    • More secondary generalization than hippocampal sclerosis
    • In general, same ictal manifestations and auras as those with hippocampal sclerosis
• Endofolium Sclerosis:
  • Neuron loss and gliosis confined to the end folium

Neocortical Temporal Lobe Epilepsy (NCTLE)

• General features:
  • Older at onset of habitual seizures than medial temporal lobe epilepsy (MTLE)
  • Seizures are shorter than MTLE
  • No seizure free interval once it is initiated
• Clinical manifestations:
  • Déja vu
  • Jaime vu
  • Depersonalization
  • Forced thinking
  • Autoscopy
  • Automatisms of the contralateral arm; bilateral upper extremity automatisms
  • Heightened sensitivity
  • Psychical
  • Experiential
  • Often normal MRI
  • Vertigo or tinnitus
  • Auditory hallucinations

Seizure Onset

• Motionless stare
• Upper extremity automatisms (ipsilateral to seizure focus)
• Dystonic posture of contralateral arm
• Bilateral upper extremity automatisms
• Contralateral tonic or clonic activity of the face or extremities; never an early manifestation of seizure

General-Differential features between MTLE and NCTLE

• MTLE:
  • Fear
  • Visceral sensations
  • High frequency of bitemporal interictal epileptiform abnormality
• NCTLE
  • Psychical
  • Experiential
  • More frequently contralateral (from the seizure focus or bilateral automatisms than ipsilateral)
  • Normal MRI
  • Neocortical TLE; well lateralized interictal EEG

Epileptic Forced Thinking

• Forced thinking definitions:
  • Recurrent intrusive thoughts, crowding of thoughts
• Differential diagnosis is temporal lobe vs frontal lobe origin

Differential Diagnosis of Epileptic Forced Thinking:

• Obsessive thoughts
• Auditory hallucinations
• Auditory perservations
• Temporal lobe limbic illusions (new thoughts not previously experienced)

Clinical features of frontal lobe forced thinking

• Speech arrest
  • Seizure of motor language areas (primarily Broca's)
  • Speech arrest or disturbance with intrusive thoughts (urge to shout)
• Forced thoughts less stereotypic (whatever words or thoughts used by the patient at time of the seizure)
• Variability of thought
• Context dependency
• Experiential imagery characteristic

Clinical features of temporal lobe forced thinking

• Depth electrode stimulation of the amygdala induces:
  • Emotional immediacy
  • Perceptually vivid features
  • Emotional tone in response to remembering
• Temporal lobe forced thinking
  • Out of context to environment prior to the seizure (a need to think of letters that begin with "L"; need to think of numbers)
• Obscene thoughts:
  • Patient feels a need to resist or negate the irrational thought
  • Obsessive-compulsive status epilepticus
    • Temporal limbic focus
  • Temporal limbic seizure focus may spread:
    • Through the uncinate funiculus and cingulum to the frontal lobe
    • Connects the frontal anterodorsal convexities to the temporal lobe

Unusual Manifestations and Localizing Value of Specific Clinical Presentations of CPS

Cardiac Arrhythmia (Anterior Insular Cortex)

• Supraventricular tachycardia
• Sinus tachycardia (L temporal lobe insular cortex)
• Sinus bradycardia (L temporal lobe/ insular cortex)
• Sinus arrest
• AV block
• Rarely accompanying chest pain
• SUDEP (sudden unexplained death in epileptic patients)

Aphasia caused by seizure in the fusiform gyrus

• Fusiform gyrus
  • Basal temporal language area; primarily like Wernicke's; unable to name categories of objects
• Speech disorders in TLE:
  • Paroxysmal dysphasia (Wernicke's area)
  • Speech automatism
• Paroxysmal dysphasia
• Wernicke's area (left side); receptive aphasia
• Speech automatism (either side)
• Functional link between left fusiform gyrus and Wernicke's area

Reproductive Dysfunction

• Left TLE
  • Polycystic ovaries
• Right TLE
  • Hypothalamic amenorrhea
• Decreased pulsatile LH (Luteinizing hormone); locus can be either side

Differential Diagnosis of TLE

• Facial blankness and staring may resemble absence seizures
• CPS vs affective psychosis:
• TLE associated with:
  • Geshwind's Syndrome (CPS personality traits)
    • Schizoid (bilateral temporal lobe involvement)
    • Hyperreligious (three religious conversions)
    • Hypergraphia (lists of every seizure event)
    • Viscous (unable to terminate appropriate question or a personal interaction)
  • Rarely TLE manifests:
    • Hallucinations
    • Agitation, anger, fear, irritability and confusion
    • Usually these are of short duration, stereotyped and intermittent
    • Associated with speech arrest, impaired consciousness and autonomic phenomena
    • Patients have insight that symptoms occur incongruously
• TLE versus episodic dyscontrol syndrome:
  • Episodic dyscontrol syndrome:
    • Uncontrolled rage
    • Occurs with provocations
    • Out of character for the patient
    • May have central nervous system deficits
    • May have documented seizures
    • May lose minutes to hours
    • Followed by fatigue and confusions
    • Often amnesia for the event
    • Violence against individuals is common
  • CPS:
    • Personally directed violence (very rare)
    • Stereotyped
    • Associated signs and symptoms of seizure activity
• Migraine with abdominal pain and nausea vs TLE:
  • In children with migraine; the abdominal symptoms may be associated with headaches
  • TLE, the abdominal auras are followed by impairment of consciousness or other epileptic phenomena
• TLE versus cardiac arrhythmia:
  • Anterior insular cortex CPS may cause chest pain and cardiac arrhythmia that may be difficult to differentiate from cardiac disease
  • TLE:
    • Attacks are not associated with usual cardiac precipitants
    • Associated with other epileptic phenomena
    • Impairment of consciousness
    • Post ictal phenomena (fatigue, thirst, headaches)
    • Chest pain not in a cardiac distribution
• TLE vs syncope (vago vagal)
  • Clinical characteristics of vago vagal syncope:
    • Characteristic pallor
    • Precipitating event (for vago vagal; specific sight or stress)
    • Slow pulse (less than 40 beats per minute)
    • Less than 30 seconds in duration; usually lasts less than 10 seconds
    • No confusion or other post event phenomena
    • May have few myoclonic jerks
• TLE vs vaso depressor syncope:
  • Vaso depressor syncope clinical characteristics:
    • Precipitating event (prolonged bed rest; hypertensive medications, upright posture, prolonged parade rest on a hot day)
    • Rapid pulse
    • No confusion
    • May have occasional myoclonic jerks

Special Aspects of TLE

• Reproductive Dysfunction:
  • 50% of women with TLE
    • Have sexual dysfunction
    • Hormonal abnormalities
    • 14–20% have amenorrhea
    • Fertility reduced by 30%
  • Men with TLE
    • Approximately 50–70% have sexual dysfunction (lack of libido)
    • Rarely satyriasis occurs
  • Associated reproductive conditions reported in TLE
    • Hypogonadotrophic and hypergonadotropic hypogonadism
    • Functional hyperprolactinemia
    • Polycystic ovary disease
    • Anovulatory cycles
• Prolactin surge after medial temporal lobe seizure:
  • Levels peak approximately 20 minutes after the seizure
  • Often elevated, but frequently no baseline measurements are available to make this determination accurately
  • Amygdala has a direct connection to the VM (ventromedial) nucleus of the hypothalamus
    • Post ictal elevation of hypothalamic releasing and luteining hormone have been noted
    • Post ictal psychosis with CPS
    • Post ictal bradycardia and asystole after CPS
    • Post ictal aphasia (basal temporal area)

Interictal personality traits of TLE

• Diagnostic specificity and validity of specific personality traits in TLE is controversial
  • Existence of these traits in patients with other seizure disorders
  • Prevalence is variable
  • Common in general population
• Noted interictal traits:
  • Catastrophic overemphasis (left temporal lobe)
  • Ideational traits (left temporal lobe)
  • Overly emotional (right temporal lobe)
  • Denial (right temporal lobe)
  • Inclusiveness
  • Hypersexuality (rare); usually hyposexuality
  • Dependence
  • Obsessive/compulsive behavior
  • Hypergraphic
  • Hyperreligious
  • Oppressiveness
  • Hypermorality
  • Circumstantiality
  • Philosophical interests
• TLE personality traits and psychopathology:
  • Most adult TLE patients are well adjusted and functional
  • Personality traits noted primarily with bilateral temporal lobe involvement
• Dual pathology causative of the personality disorder (ipsi or contralaterally)
  • Medial temporal sclerosis with migrational disorder
  • Mirror foci (frequent seizures; interictal spiking)
  • Trauma (bilateral temporal lobe involvement)
  • Surgery on one temporal lobe; remaining temporal lobe dysfunctional
  • X-ray (particularly for pituitary tumors)
  • Viral involvement (Herpes Simplex encephalitis)
• Klüver–Bucy Syndrome:
  • Hyperorality: all objects are placed in the mouth
  • Hypermetamorphopsia: all objects are examined with the same degree of interest and intensity
  • Short term memory deficit
  • Hypersexuality (attempted intercourse with same sex or inanimate objects)
  • Sham rage: trivial provoking events; anger reaches maximum intensity instantly; patient returns to baseline immediately

Psychopathology

• Patients with seizure disorders have a higher incidence of psychiatric disorders than a control population
• Psychosis resembling paranoid schizophrenia reported in TLE patients
  • Better preservation of affect in TLE vs schizophrenia patients
  • Less personal isolation than schizophrenic patients
• Temporal lobectomy may cause:
  • New onset of psychosis
  • Improvement of instability and aggressiveness
• Aggressive violent behavior in TLE:
  • Non-directed
  • Short lived
  • Fragmentary
  • May be a stereotyped manifestation of some temporal lobe seizures
• Predictive variables of interictal psychosis in epilepsy
  • Earlier age at onset of epilepsy
  • Family history of psychosis
  • Borderline intelligence
  • CPS and GTCS are seizure type

Amnesia in TLE patients

• Short term memory loss (dysfunction of medial temporal lobe structures)
• Defect in confrontational naming
• Decreased word fluency

Temporal Lobe Pathology

Glioma, arteriovenous malformations, cavernous hemangiomas, hematomas or traumatic scars all cause complex partial seizures. The advent of MRI scanning with associated volumetry of medial temporal lobe structures and the hippocampal formation as well as PET, SPECT, and MRI spectroscopy have provided a much better understanding of congenital abnormalities that underlie these conditions. There are a variety of migrational disorders that can be diagnosed by MRI scanning. These are caused by abnormal neuronal migrations of germinal plate neurons from the ventricle to the cortex and disrupted gyration and apoptosis of the neurons that have migrated. Nests of subependymal neurons are noted in the frontal, parietal and temporal white matter, in periventricular heterotopia. This may be seen unilaterally or bilaterally. The walls of the ventricles demonstrate nodules of subependymal neurons that have not migrated. Radial glial fibers from the ventricles to the cortex may be seen in tuberous sclerosis. Migration of these subependymal cells occurs in the 20–22nd week of gestations. A double cortex or thickened band heterotopia may be seen in those patients who have suffered failure of apoptosis and no remodeling of the cortex. The extremes of this condition are schizencephaly and lissencephaly. Failure of architectural remodeling may be seen in focal cortical dysplasia in which the orderly laminar structure of the cortex is disrupted. These focal dysplasias may be further characterized as a laminar heterotopia, simplified gyral pattern and focal microgyri. There are genetic syndromes with X-linked heterotopias and double cortex as well as sporadic genetic forms of abnormal migrational patterns. Agyria, polymicrogyria, macrogyria, and sublobar dysplasias have all been seen with complex partial seizures of temporal lobe origin. Focal cortical dysplasia may demonstrate abnormal giant neurons and balloon cells in a addition to the dysmyelination.

The syndrome of medial temporal sclerosis is suspected if the patient has suffered prolonged febrile convulsions as a child. Medial temporal sclerosis may also be seen in conjunction with migrational defects a situation known as dual pathology. Bilateral anatomic abnormalities with a unilateral temporal lobe seizure focus have been seen in 20–40% of patients with medial temporal lobe sclerosis. Mesial temporal sclerosis may extend throughout the temporal lobe and involves both the cortex and white matter. The temporal pole is frequently atrophic ipsilateral to the side of seizure onset in seizure patients.

Bilateral parasagittal, parieto-occipital and episylvian, polymicrogyria as well as hemi megacephaly are other patterns of cortical dysplasia. These migrational defects are frequently associated with contralateral hemiasymmetry of the arms, face and leg. If the face is obviously involved, the process is termed the Parry–Romberg Syndrome. If the seizure disorder is associated with an intrauterine stroke of a vascular territory, severe trauma a porencephalic cyst or arteriovenous malformation, the contralateral hemiatrophy is severe and obvious. Limbic encephalitis not associated with neoplasm is a cause of temporal lobe seizures. Perivascular lymphocytic infiltration is noted. The CSF demonstrates a mild pleocytosis. IgG is demonstrated in 20% of patients and oligoclonal bands in 50%. The differential diagnosis includes Rasmussen's encephalitis, Hashimoto's disease, SLE and paraneoplastic limbic encephalitis.

Perivascular clustering and cortical neuronal clustering (micro dyseneias) is associated with mossy fiber sprouting into the dentate supragranular layer. Congenital porencephaly may absorb concordant with hippocampal sclerosis.

Insular Cortex Seizures

• General features:
  • Hippocampal seizure foci spread to the insular cortex; general afferents from and efferents to:
    • Amygdala
    • Enterorhinal cortex
    • Hippocampus
    • Cingulate cortex
    • Orbito frontal cortex
• Clinical symptoms:
  • Respiratory
    • Modulates the amplitude and frequency of respiratory movements
    • Chest fullness is experienced
  • Viscerosomatic
    • Chest constriction ascending to the anterior cervical region; associated with nausea
    • Abdominal constriction and heaviness
    • Intense distressing abdominal pain
    • Throat constriction
  • Somatosensory (opposite the side of the focus)
    • Ascending retrosternal sensation of heat
    • Brisk nonpainful heat sensation of the trunk and both upper and lower limbs
  • Oroalimentary manifestations
    • Chewing and swallowing
    • Mastication

Division B: Fontal Lobe Seizures

General Clinical Characteristics

Fontal lobe seizures begin abruptly, are often brief, are associated with minimal post ictal confusion, come out of sleep and may occur in clusters. The clinical features depend on the areas of the frontal lobe that are affected. Seminal features are motor, automatisms, and vocalization.

Frontal Lobe Seizures

• General Characteristics
• Genetics: ADNFLE; autosomal dominant nocturnal frontal lobe epilepsy (chromosome 20)
• Clinical features of localization related frontal lobe seizure:
  • Prerolandic cortex (area 6)
    • Speech arrest or impairment
    • Tonic-clonic movement of contralateral face
    • Repetitive swallowing
    • Contralateral flaccidity without movement (suppressor strip of Hines)
  • MI (area 4)
    • Jacksonian march; mouth and thumb are affected early; motor neurons here have a wide area of representation and low threshold; often the thumb and corner of the mouth initiate the march
    • Rapid secondary generalization particularly if the focus is in MI or SI
    • Occur during sleep
    • May occur in clusters
    • Inferior second frontal convolution (Broca's area) cause speech arrest, stammering or stuttering with the seizure
    • Seizures often are brief less than 75 seconds
    • No prolonged ictal state
    • Movements occur with progression of the seizure
    • Bilateral purposeful and non-purposeful movements (motor automatism-bicycle pedaling)
    • High monthly seizure rate
    • Motor arrest
• Supplementary motor area seizure (SMA):
  • SMA area eight of the frontal cortex
  • Brief
  • May cluster at night
  • Preservation of consciousness
  • Speech arrest
  • Vocalization
  • Fencing posture: extended contralateral arm; flexed ipsilateral arm; contraversive head and eye movement
  • Versive movement away from the side of ictal onset
  • Sudden paratonic posturing of one or more extremities
• Cingulate cortex:
  • Aura; fear and panic
  • Emotional outbursts
  • Increased sympathetic tone
  • Complex motor, gestural, or automatic manifestation with change of mood and affect
• Orbitofrontal cortex:
  • No aura until the seizure spreads into the cingulate or insular cortex
  • After the spread:
    • Autonomic signs
    • Olfactory hallucinations and illusions
    • Oroalimentary auras
    • Can have persistent vocalization
    • Violent dramatic automatisms
    • Motor and gestural automatisms
• Dorsolateral prefrontal cortex:
  • Tonic posturing of head and upper extremities
  • Contraversive head and eye movements
  • Clonic facial contractions (rare)
  • Speech arrest
• Frontal eye field (FEF areas 8, 10):
  • Head and eye turned side away from the lesion
  • Horizontal jerk nystagmus to the contralateral side
  • Often impaired consciousness
  • Pupillary dilatation of the contralateral eye (early at onset)
• Paracentral lobule:
  • Tonic movement of the ipsilateral foot
  • Contralateral leg involvement
• Opercular areas:
  • Ipsilateral clonic facial movements
  • Mastication, salivation, swallowing
• Frontopolar cortex:
  • Vocalization
  • Hyperventilation
  • Truncal flexion
  • Complex gesture automatisms
  • Sudden awakening after seizure
  • Bimanual/bipedal automatisms
  • Forced thinking
  • Axial clonic jerks (that may cause falling)

Extra Frontal Seizure:

• Behavioral arrests or automatisms typically precede head deviation

Hyperkinetic Frontal Lobe Seizures:

• Location of seizure focus:
  • Orbitofrontal cortex
  • Dorsolateral prefrontal cortex
  • Frontomesial cortex
• Clinical features:
  • Complex bimanual and bipedal movements
  • Kicking, thrashing, clapping, rubbing
  • Sexual automatisms
  • Autonomic hyperactivity (piloerection, pupillary dilatation, micturition)
  • Preserved consciousness
  • Usually positive EEG correlate
  • Status epilepticus

Division C: Parietal Lobe Seizures

Simple partial sensory seizures are usually of parietal lobe origin and often relate to lesions in specific components of the sensory homunculus. Abnormal tongue sensations (coldness, stiffness, numbness) are often bilateral. This may also occur with thalamic lesions (VPM). A patient's awareness of a sensory deficit in 1/2 of the tongue suggests an intraparenchymal brainstem lesion. Fifth nerve lesions from collagen vascular disease such as scleroderma and Sjögren's disease are usually perceived as numbness. Commonly cervical plexus (posterior roots of C2, C3 – the preauricular nerve) may also cause tongue (unilateral) numbness. Bilateral facial paresthesias and numbness may also emanate from SI.

Other positive sensory phenomena emanating from the parietal lobe are the feeling that a body part is being moved or the patient has a desire to move the body part. Nondominant parietal sensory sensations from seizure activity manifest the feeling that a body part is absent. Inferior and lateral parietal lobe seizures may cause feelings of nausea, choking or sinking. Inferior parietal lobe seizures may cause a feeling of the body being tilted or severe disorientation in space or vertigo (intraparietal sulcus). Seizures from this area may also cause epileptic skew deviation (Brodmann's 19/37/39 and 40) Bilateral heat sensations arising from the feet and sweeping upwards over the body and may emanate from SII (that is at the base of SI). SII seizures may also be associated with poorly localized cold and pain. These sensations may be bilateral, contralateral or ipsilateral to the seizure focus. Dominant parietal lobe seizure activity may cause a receptive or conduction aphasia. Painful contralateral parietal lobe auras have been described.

Division D: Febrile Convulsion

Definition: A seizure occurring in infancy and childhood that occurs between three months and five years of age in association with fever, but without evidence of intracranial infection or defined cause.

General features

• Just one febrile convulsion in the majority of children less than three years of age (18–22 months; boys > girls)
• Usually generalized clonic-tonic; may be of any type
• Low incidence of acquired motor or intellectual abnormality following a febrile seizure; low mortality rate
• Recurrences:
  • Approximately 1/3 of children have recurrence; 12–15% of these children have further recurrences
  • Risk factors for a recurrence:
    • Age of onset of first febrile seizure less than 13 months of age 2:3 chance of developing recurrence
    • 14–22 months of age, 1:2 chance of recurrence
    • Greater than 32 months, 1.5 risk
    • 75% of recurrences within one year; 90% within two years
• Risk of developing epilepsy after febrile seizure four times the control population
• Risk for developing epilepsy after a febrile convulsion:
  • Seizure duration greater than 15 minutes
  • Greater than one seizure in 24 hours
  • Focal features of the seizure
  • Prior neurological deficit before febrile convulsion. Increased risk of epilepsy by age seven is 3× control population
  • Not established that children with recurrent febrile seizure have increased risk of epilepsy
  • Increased risk of epilepsy if febrile seizures began in infants of 6 months, 5.7% vs 1.5% after the first year
  • Family history of febrile convulsions not established as a risk factor for development of epilepsy
• Genetics: GTCS +febrile convulsions
  • Chromosome – gene