Where am I ?Interhospital Geriatric Meeting

Dr. SL Kwok / Dr. YF MakQueen Elizabeth Hospital

Case 1Mr. XM/75referred from GP for sudden onset of confusion and memory loss suspecting of acute stroke

backgroundNKDARetired taxi driverNon smokersocial drinker (small amt of beer / wine at occasions)Lives with wifeWalks unaided, ADLI5-6 years of formal schooling

Past medical historyHT

Adalat R 20mg bddyazide 1 tab daily

Eczema on aqueous cream and prn piritonFU GOPDotherwise good past health

History of presenting illnessPresented with sudden onset ‘confusion’ and memory loss on the day of admissionno Hx of background memory lossNoticed by wife sudden memory loss and abnormal behaviour on the day of admissionDid not remember what he did that morning after leaving home for morning exerciseAlso cannot recall events in the preceding few days on admission

Daily routineget up from bed at ~ 06:30go out for morning exercise at ~ 07:30go to restaurant after exercise, usually at ~ 08:30go to market to buy food for the daybuy newspaper and get the letter from the mailbox, and be back to home by ~ 10:30

What happened ?on the day of admission

go out of home for morning exercise as usualbut back home later than usual, at noonWith the food, letter but not the newspaperpatient cannot provide a detail account to wife of why he come latepatient did not recall some recent event including his BIL admitted to hospital, his son is going to get marry and he had played mahjong 2 days ago

Go to restaurant to meet his friends as usual, appear to be normal and chat with them and comment on recent news appropriately He was also seen by his friend in the market at usual time, appear to be normal

History of presenting illness (con’t)

No witnessed convulsionNo other associated symptoms including fever, dizziness, headache, weakness, numbness, slurring of speech or swallowing difficultyNo facial asymmetry was notedNo intake of other drugs besides the antihypertensivesNo previous head injuryCompletely normal the day before

History of presenting illness (con’t)

BIL recently admitted to hospital for illness for ~ 10/7, currently in a critical condition and may succumb used to have good relationship with his sister and brother-in-law and visit them frequentlypatient is mildly affected by this incidence and appear to be absent-minded latelyforgot to turn off tap occasionally after that incidence, but no background memory loss

History of presenting illness (con’t)

Patient was bring to GP clinic for consultationpatient keep repeatedly ask why he was taken here and there, what he was doing, what’s the time and where he was

Physical examinationGCS 15/15, orientedPower full over 4 limbsNo cerebellar signsCN intact Speak coherently and appropiatelyNo carotid bruitChest clear /CVS / abd unremarkable

InvestigationsECG SR no ischemia or arrhythmiaCBP normalRLFT normalRandom glucose 5.6TG 1.3 / TC 5.3 / LDL 3.1TSH normal

VDRL : non reactiveB12 : 278Folate : 25.4urine toxicology : metabolite of piriton onlyS/B EEG (2/2) : no epileptiform activitiesMMSE : 29/30

CT brain 1/2/10No focal abnormal brain parenchymal attenuation.No acute hemorrhage.No extra-axial fluid collection.Ventricles are normal in size and shape.No discrete space-occupying lesion seen.repeated CT brain 3/2/10 no serial changes

Case 2

Mr. YBring by wife to AED after presented with acute onset of ‘confusion’ and abnormal behaviour

Background

M/67Non drinkerHx of high BP, seen herbalist on herbal remediesotherwise good past health

What happened ?

back to home at ~ 2:00pmappear normal initially when he come back homego to turn on the hi-fi and play some musicbecome confused around 1/2 hr later

found the home appear untidy to him, with all his CDs and hi-fi component being not in the usual order, but in fact nothe go to pour out all his CDs onto the floorasking who make the messappear to retain his own identity and where he isthen the home environment suddenly appear tidy again to him, asking who have just tidied up the place

then c/o facial flushingBP taken by wife at that time 178/114a few repeated measuring showing similar readingpatient then rushed to toilet and turned on the water tap with water pouring onto his head, and patient claim he want to 'cool down himself'patient repeatedly asking wife to repeat measure BP for him, claiming that she had not done it yetno prior history of similar episode

The next day

Patient become normal againcan only recall the detail when he initially go back homecannot recall the key event which resulted in this admissionhowever the memory before and after were very clear to himhe can even recall which CD he played before the eventdenied drug or alcohol use

Physical examination

GCS 15/15 on admissioncoherent speech and obey commandFull powerCranial nerve intactNo cerebellar signabd softCardiovascular / chest / abdominal exam unmarkable

Investigation

CBP normalRLFT normalFasting glucose 5.3urine toxicology -veTG 0.8 / TC 5.5 / LDL 3.8

CT brain : No focal abnormal brain parenchymal attenuation.No acute hemorrhage.No extraaxial fluid collection.Ventricles are normal in size and shape.No discrete space-occupying lesion seen

S/B EEG : (prelim report) no sharp waves, symmetrical normal background

Transient global amnesia

IntroductionA clinical syndrome of reversible anterograde amnesiaAnterograde amnesia : inability to form new memoryrepetitive questioningoccurs in middle-aged and elderly individuals

First described in 1956 in 2 case seriesThe term ‘Transient Global Amnesia’ was introduced and been used since 1964However, the exact etiology and pathophysiology is still not completely understood up till now

Epidemiologyincidence

General population : 3-8 / 100,000 > 50 years old : 23.5-32 / 100,000

majority of episodes occur in individuals between the ages of 50 and 80mean age of onset : 60-65No sex predilectionAssociation with migraine in some case

PathophysiologyPrimary site of involvement is the mediobasal temporal lobe and hippocampus involved in the formation and retrieval of new episodic memoriesSupported by neuroimaging

DWI-MRI studies in acute and subacute stages of TGA demonstrated lesions in the hippocampushigh resolution imaging studies have specifically implicated the CA-1, Sommer sector

Pathophysiology (con’t)Lesions are most often unilateral and left-sided, but right-sided and bilateral lesions also occurdominant-side hippocampal lesions : prominent verbal memory loss nondominant hippocampal lesions : prominent visuospatial memory deficits

EtiologyRemained uncertainNo single cause can fully explain the whole clinical pictureProbably multiple causesHypothesis

Arterial ischemia Venous congestion Migrainous phenomenon Epileptic phenomenon

Arterial ischemia -- prosHad some similar feature with TIA

Occur in older adultUsually resolve within 24 hrs

Reported in setting with thromboembolic riskvertebral artery angioplasty and stenting basilar artery thrombosis aortic dissection hypercoagulable conditions

Hippocampus represent a watershed area between two major arteriesDWI-MRI signal abnormality in hippocampus are often described in patients with TGA

Arterial ischemia -- consDifference in some clinical features

TGA episodes are longer in duration than typical TIAs TGA patients have a lower atherosclerotic risk burden than patients with TIApatients with TGA have a lower risk of future stroke and death, and resembles that of an age-matched populationTGA appears to be precipitated by events that are not associated with TIA (eg. Valsalva maneuver)

Arterial ischemia -- consDWI MRI finding

DWI lesion are not specific to only TIA / strokelesions were no more common in TGA patients than in age- and sex-matched controlslesions seen in TGA are somewhat atypical of those seen in TIA

TIA had larger lesionsTIA are more likely to be observed in the first few hours of symptoms onsetTIA are more likely to evolve into a permanent T2 abnormality

Venous congestion -- pros Trigger event

Valsalva maneuvervigorous activity of the armssympathetic activation from acute emotional eventscold water immersion

increases in either intrathoracic pressure or venous return could lead to central venous congestion affecting the deep venous system that drains the dorsomedial thalamus and hippocampus

Venous congestion -- prosDoppler USG studies indicate TGA patients are more common to have jugular valvular insufficiency with demonstrable venous reflux

Venous congestion -- consside of apparent valvular insufficiency did not always correlate with the dominant side of venous blood flow or with the lateralization of DWI lesionsQuestions unanswered :

Why the venous congestion and/or ischemia is selective to the anatomic structures related to memory Why TGA isn't seen more frequently with venous sinus thrombosis Why recurrence is so infrequent if the abnormality can be induced by a Valsalva maneuver Why it only occurs in older adults

Migrainous phenomenonPros

Studies demonstrate association with migraine

Consyounger age group in migraineMigraine is typically a recurrent disease

Clinical featuresProminent anterograde amnesia (inability to form new memories)

May appear to be disoriented in time or placeoften repetitively ask questions about the date or their environmentImmediate recall (eg, digit-span) is intactdelayed recall is impaired

Retrograde amnesia is commonmore variablecan extend back hours to days, weeks, and rarely years

Other cognitive functions are sparedable to perform complex motor tasks during spell such as driving, cooking, lecturing, and playing a musical instrumentmean duration of episodes is approximately six hours, most last between 1 and 10 hours

When the spell resolvesthe retrograde amnesia usually completely resolves or is isolated to a brief time immediately preceding the eventPatients are left with an amnesic gap for the main episode

Associated symptomsheadache (10-40%)Nausea, nonspecific dizziness, anxiety, paresthesias

Triggering eventacute emotional eventschronic emotional stress physical events (eg, strenuous activity, sexual intercourse, Valsalva maneuver)postural changesmedical procedureshigh altitudecontact with water and/or changes in body temperature

Prior episode is unlikely, < 5%Physical exam is usually unremarkable

DiagnosisBased on clinical featuresNo confirmatory diagnostic testExclude possible differential diagnoses

Diagnostic criteria

Lancet Neurol 2010; 9: 205–14

Differential diagnosesSeizure TIA / stroke

Stroke syndrome presenting with isolated amnesia without other focal neurological symtpoms is associated with lesion in the mesial temporal lobe, caudate nucleus, cingulate gyrus, and splenium of the corpus callosum

DeliriumUsually a more global confusion and inattention

Differential diagnosesOther possible differential diagnoses

Head injuryanoxic event (carbon monoxide exposure)HypoglycemiaIntoxicationdrug or alcohol withdrawalherpes simplex encephalitis

Proposed diagnostic criteria

Information about the beginning of the attack is available from a capable observer. This is to exclude head trauma or loss of consciousness at the onset. Clouding of consciousness or loss of personal identity should be absent. Patient should be examined during the attack to be certain that there are no accompanying neurologic signs or symptoms besides antegrade amnesiaThe memory loss should resolve within 24 hours. Epileptic features must be absent. Patients with active epilepsy are excluded

InvestigationNo specific diagnostic test availableAim to exclude possible DDxAppropriate initial workup

Serum electrolyteGlucoseToxicology screeningBrain imaging eg. CT

Further evaluation depend on clinical suspicion including EEG, especially recurrent episodes

TreatmentNot necessary in clear case of TGAAdvised to observe patient in hospital until the episode subsidedTreatment may be necessary if alternative diagnoses is identified eg. CVA / seizure

PrognosisUsually recover without any neurological deficitRecurrent rate is low : annual rate is estimated to be 2.5-5.8%However, recent studies found that residual memory deficit may occur in patient with TGA

high-resolution T2-reversed MRI of the hippocampus showed a significantly higher frequency of cavities in the hippocampus than controls, suggesting permanent neuronal loss in the Sommer or CA1 sectorsubclinical residual deficits may be common one or more years by neuropsychologic testing