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Neuro-Psychiatric and Cognitive Impact of Tick-borne Disorders on Children and Adolescents
Rosalie Greenberg, MD, FAPA, DFAACAPChild and Adolescent Psychiatrist
Summit, New Jersey
• PA Lyme Medical Conference 2018New Frontiers in Lyme and Related Tick-Borne DiseasesApril 6-7, 2018
PA Lyme Medical Conference 2018New Frontiers in Lyme and Related Tick‐Borne Diseases
The Hershey Lodge, Hershey, PAApril 6‐7, 2018
Disclosure Statement
• I do not have any financial arrangements or affiliations with any commercial entities whose products, research, or services may be discussed in these materials.
Outline
• General info re LD in youth• Neurologic symptoms• Cognitive issues• Psychiatric symptoms• Findings in 27 bipolar youngsters• Co‐infections • Caveats• Conclusions
Lyme in Children
According to the CDC:
• Most common among boys 5‐19 years old
• Kids have 3x the rate of all other age groups
• 25% of Lyme cases are in children
Clinical Manifestations of BB
• Localized skin infection at bite site (erythema migrans or bullseye rash)
• Development of flu‐like symptoms:fevermalaisearthralgiasmyalgias
One third or more don’t recall a rash and flu‐like symptoms could have been very mild
LD in ChildrenCan be hard to recognize:
Kids often get colds and feverSomatic complaints common in kids• “growing pains”• headaches • problems with concentration
Behavioral. emotional, and subtle cognitive changesmay occur
LD onset in childhood
Can interfere in multiple spheres:
Physically (sports)Cognitive Development (Academic progression)Mentally/EmotionallySocially
Lyme Disease in the general population
•15‐40%developneurologicproblems
• CoylePK:Neurologiclyme Disease.Semin Neurol 12:200‐208,1992).
Lyme
• Children have CNS involvement more frequently than PNS involvement‐• Peripheral neuropathy occur in 1% to 3% of kids
• Most common PNS manifestation is Bell’s palsy with a sudden onset of facial palsy
‐ Bilateral facial palsy in 6% to 37%
• Kids are bitten by ticks more frequently around head and neck making them more vulnerable to CNS infections
• Neuropsychiatric symptoms are often misdiagnosed• And perhaps underdiagnosed
Neurologic Manifestations in ChildrenN=94 • Headache 71%• Facial Palsy 14%• Sleep Disturbance 7%• Papilledema 7%• Diplopia 2%• Paresthesia 2%• Carpal tunnel syndrome 1%• Guillain‐Barre like syndrome 1%
Belman et al. Neurology 1993
Neurologic Lyme in Children(N=94)
• Onset of neuro problems 1.5 wks‐51 months after initial systemic signs of LD
• Majority presented within 12 months of infection
• Belman et al. Neurology 1993
Lyme Disease and the Central Nervous System in Children
•The little literature available has focused more on cognitive effects
Cognitive effects of LD in Children
• N=41 children that were rx’d with antibiotics vs. 14 controls with subacute rheumatological diseases vs. 23 healthy sibling controls
• Looked at predisease and post disease academic scores; performed of neuropsych testing and found no perceived long‐term deterioration in cognitive or personality areas as reported by parents
• But this may not represent all kids with LYD, as most had presented with rheumatologic sx and received early rx (i.e. didn’t present with other LD and didn’t receive early treatment)
• *Adams WV et al 1994
Chronic Lyme in Youth
• Case series 12/86 14% developed psychiatric and cognitive difficulties in the areas of attention and memory
• *Fallon et al. Neuropsychiatric Aspects of Lyme Disease in Children. Presented at the 12th International Conference on Lyme Disease and other Spirochetal and Tick‐Borne Disorders, NY April 1999
Controlled Study of Cognitive Deficits in Children with Chronic Lyme Disease
(Tager et al 2001)
N=20Deficits in visual and auditory attentionDeficits in working memory and mental tracking
Cognitive Problems Associated with TBI
Include difficulty with:1. attention and concentration2. speed and efficacy of processing info3. learning and memory4. auditory processing and language expression5. planning and organization6. multitasking7. math and reading scores often significantly lower than their verbal and non‐
verbal intellectual abilitiesShea, LJ, and Leventhal, JG The role of neurospsch testing in children with lyme disease (website). 2014
Neuropsychological Symptoms of TBD In Children• Harder to recognize
• Tick bite may be unknown• Regression in children harder to recognize
• Somatic complaints common in kids“growing pains”, headaches, problems withconcentration
• The more common and yet more subtle manifestation may be in the emotional, cognitive and behavioral sphere
TBI related Neuropsychological Symptoms
• Index of suspicion crucial (Yogi Berra principle)
Lyme Encephalopathy
• It is one of the most common neurologic presentation of late LD Includes disturbances of:• Memory (problems with short term memory, word finding)• Attention (slowed processing speed) • Sleep• Mood (irritability, emotional lability)• Marked fatigue• Dyslexia• Spatial discrimination
Coyle PK. Neurologic Lyme disease. Semin Neurol. 1992Tager,F and Fallon BA. Psychiatric and cognitive features of Lyme disease. Psych Annals 2001
CDC study in New JerseyN=64 school children
• Medium duration of illness at time of interview=363• Medium # school days missed =103 (2‐548)• Median duration of home instruction 5‐792 days• 78% had a fall in grade point average
Neuropsychiatric Symptoms of TBI
• Hypotheses
• Youth with neuropsych symptoms (especially non‐cognitive sx‐i.e. emotional and behavioral sx) of TBI are often misdiagnosed
• These neuropsych symptoms may be a presenting and much common manifestation of TBI in children
Mood Symptoms in a Controlled Study of Cognitive Deficits in Children with
Chronic Lyme Disease
N=20Parent/child‐reported psychopathology. • Regarding depression parents indicated: 41% (7/17)had suicidal thoughts and 11% (2/18) made a suicidal gesture.
• On child rating (CDI) 40% (8/20) had suicidal thoughts
• (Tager et al 2001)
Neurologic Lyme in Children(N=94)
36 kids or 38% had behavioral or mood changesIrritabilityMalaiseEmotional labilityAttentional issuesDecreased interest in play
(Belman et al. Neurology 1993)
Children with Chronic LD have higher rates of Anxiety, Mood, and Behavioral Disorders than Children without LD
(Fallon BA, Tager FA, Rykiel R: Neuropsychiatric aspects of Lyme disease in children. Abstract book, 12th International Conference on Lyme Disease and other Spirochetal and Tick‐Borne Diseases, New York, NY April, pp30‐31.)
TBI and Psychiatric Symptoms
Potential Psychiatric Symptoms of Lyme/TBI
• Psychosis• Attention Deficit Hyperactivity Disorder• Anxiety / Panic attacks• Depression• Bipolar disorder• Autistic Spectrum Disorder• Obsessive Compulsive Disorder• Violent behavior / Irritability• Suicidal thoughts• Sleep disorders• Cognitive Problems
Studies have shown that TBI has been associated with a myriad of Psychiatric Symptoms –
But
What about the Converse?
Infections and Mental Illness
•Although many infections can precipitate psychiatric symptoms, the question is also how often are psychiatric symptoms or syndromes the result of infections?
TBI and PBD Sample Characteristics(N= 27)
• 22/27 (81%) boys• 5/27 (19%) females• Average age at BPD dx = 7.3 (5‐12)• 15 BPI*• 12 BPII*
*DSM IV‐TR criteria
R
Results of Testing
Results of Serologic Testing
Babesia (N=16)Mycoplasma Pneumoniae (N=11)Bartonella (N=8)Lyme (N=6)
(if include Igenex IgG WB +: Lyme = 9)Anaplasma (N=1)Ehrlichia (N=1).
Results of Serologic Testing
89 % or 24/27 were positive on serologic testing
92% (22/24) with + serology complied with recommendation clinical assessment by a specialist in TBI
Of these 92% or 20/22 were clinically diagnosed with 1 or > TBI
Summary:74% or 20/27 were diagnosed with a TBI23.5% or 4/27 were positive for PANDAS
Review of 69 consecutive patients from a Private Pediatric Psychopharmacology Practice
(2/1/15‐2/1/18)
49/49 were positive when tested by specialized labs (Igenex, Galaxy etc.)
7 were negative when tested by either Quest Diagnostics (4) orLab Corp (3) alone
6 had known TBI at the time of referral
7 did not get testing
The Problem of Multiplicity of TBI
• Still early in our understanding and without good studies separating out the individual infections
• Lyme‐ if patient has it there is a good chance that co‐infections are also present e.g.BabesiaBartonella
Babesia
• Emotional lability • Depression
Clinical manifestations of Tick Borne Illness in Children Bryant KA, et Marshall, GS; 2000
Bartonellaencephalopathypanic attacksconfusionragedepressionheadachescognitive dysfunctionpersonality disordersbipolar disorder
‐Dr. Jones Kids
Bartonella and Cognition
• Problems with working memory
• Slowed processing speed
• Small vessel disease• Goes to collagen and RBC’s
• Hypermobility syndrome
Bartonella Small Vessel Disease: CNS Features*
1. Mild cognitive impairment
2. White matter “subcortical disconnection’
3. Executive dysfunction impaired
4. NOT a dementia
5. Working memory impaired (RAM)
6. Processing speed delayed
7. Mood labile*BR Mozayeni MD
Caveats• True prevalence of TBI in the general population in study area is unknown
• Each pathogen genus (e.g. Borrelia, Bartonella, Mycoplasma, etc.) consists of a wide variety of difference species only some of which affect human hosts.
• Cross reactivity of species may interfere with intra-genus testing results
• Testing for Mycoplasma pneumoniae is confusingLeading cause of respiratory infections, but can also cause gi, cv, musculoskeletal, renal, or neurologic problems (i.e. encephalitis)1,2
1Defilippi A, Silvestri M , Tacchella A, Giacchino R, Melioli G , Di Marco E, Cirillo C, Di Pietro P, Giovanni A. Rossi GA. Epidemiology and Clinical Features of Mycoplasma Pneumoniae Infection in Children. Respiratory Medicine. 2008; (102), 1762-1768. 2 Meyer PM, Sauteur JC, Streuli, 2 Goetschel, P.Mycoplasma Pneumoniae-Associated Encephalitis in Childhood – Nervous System Disorder During or After a Respiratory Tract Infection Mycoplasma-Pneumoniae-Assoziierte Enzephalitis bei Kindern – NeurologischeSymptome im Rahmen eines Luftwegsinfektes. lin Padiatr. 2011; 223(4): 209-213.
Caveats• MP is also known to be carried by Ixodesticks
• Co‐infection with PANDAS/PANS in addition to TBI high
• Could the latter indicate a heightened susceptibility or weakened immunity in these co‐infected individuals?
Issues to Consider
• Association does not mean causality• What happens with treatment?• More sensitive to psychiatric meds?• When to stop-when does rx become more harmful
than helpful?
Conclusions
• Initial presentation of TBI in youth may be symptoms of a variety of childhood mental disorders
• Although the temporal relationship between TBI and PBD cannot be determined, the high rate of TBI in the one case series presented is provocative
• Much more research is needed to clarify the interaction of TBI and psychiatric illness – especially in children and adolescents