Editing African trypanosomiasis (section)

=== Neurological Phase ===
The second phase of the disease, the [[neurological disorder|neurological phase]] (also called the ''meningoencephalic stage''<ref name="www.cdc.gov_2020" />), begins when the parasite invades the [[central nervous system]] by passing through the [[blood–brain barrier]].<ref name="pmid15304634" /> Progression to the neurological phase occurs after an estimated 21–60 days in case of ''T. b. rhodesiense'' infection, and 300–500 days in case of ''T. b. gambiense'' infection.<ref name="www.cdc.gov_2020" />

In actuality, the two phases of African trypanosomiasis—the hemolymphatic stage and the neurological stage—often overlap, and their clinical features can be nonspecific or evolve gradually, making it difficult to distinguish them based on symptoms alone.<ref name=":03">{{Cite journal |last=Kennedy |first=Peter |date=25 January 2019 |title=Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis |journal=Frontiers in Immunology |volume=10 |page=39 |doi=10.3389/fimmu.2019.00039 |doi-access=free |pmid=30740102 |pmc=6355679 }}</ref> While signs such as enlarged lymph nodes and intermittent fever are more characteristic of the early stage, and neuropsychiatric symptoms such as sleep disturbances, confusion, or motor abnormalities suggest progression to the later stage, these indicators are not definitive. Consequently, to accurately determine the stage of the disease, specifically to determine central nervous system involvement, a [[lumbar puncture]] is performed to analyze the [[Cerebrospinal fluid|cerebrospinal fluid (CSF)]].<ref name=":03" /> The detection of trypanosome parasites in the CSF confirms that the infection has progressed to the neurological phase. This assessment is crucial because treatment protocols differ depending on whether or not the central nervous system has been affected. In the later stage, more intensive drugs that can cross the [[Blood–brain barrier|blood-brain barrier]] are necessary to eliminate the parasites from the brain and spinal cord.

==== Sleep Disorders ====
Sleep-wake disturbances are a leading feature of the neurological stage<ref name="pmid15304634" /><ref name="Maxfield_2020">{{cite book | vauthors = Maxfield L, Bermudez R | chapter = Trypanosomiasis (Trypansomiasis)|date=2020| chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK535413/| title = StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=30571034|access-date=2020-08-11 }}</ref> and give the disease its common name of "sleeping sickness".<ref name="pmid15304634" /><ref name="www.cdc.gov_2020" /><ref name="Maxfield_2020" /> Infected individuals experience a disorganized and fragmented sleep-wake cycle.<ref name="pmid15304634" /> Those affected experience [[sleep inversion]] resulting in daytime sleep<ref name="pmid15304634" /> and somnolence,<ref name="www.cdc.gov_2020" /> and nighttime periods of wakefulness<ref name="pmid15304634" /> and insomnia.<ref name="www.cdc.gov_2020" /> Additionally, those affected also experience episodes of sudden sleepiness.<ref name="www.cdc.gov_2020" />

This sleeping impairment is also related to disruptions of [[circadian rhythm]], the body's internal clock which regulates rhythmic behavior including metabolic patterns in cells.<ref name="Filipa2">{{Cite journal |last1=Rijo-Ferreira |first1=Filipa |last2=Carvalho |first2=Tânia |last3=Afonso |first3=Cristina |last4=Sanches-Vaz |first4=Margarida |last5=Costa |first5=Rui M |last6=Figueiredo |first6=Luísa M. |last7=Takahashi |first7=Joseph S. |date=2018-01-04 |title=Sleeping sickness is a circadian disorder |journal=Nature Communications |language=en |volume=9 |issue=1 |page=62 |doi=10.1038/s41467-017-02484-2 |issn=2041-1723 |pmc=5754353 |pmid=29302035}}</ref> Studies indicate ''[[Trypanosoma brucei|T. brucei]]'' alters the oscillatory expression of clock genes in the [[Suprachiasmatic nucleus|suprachiasmatic nuclei (SCN)]], among other brain regions, charged with circadian regulation.<ref name=":0222">{{Cite journal |last1=Cavadini |first1=G. |last2=Farkas |first2=I |last3=Saez |first3=M. |last4=Brunner |first4=M. |last5=Kerekes |first5=T. |last6=Jäkel |first6=M. |date=2007 |title=TNF-α suppresses the expression of clock genes by interfering with E-box-mediated transcription |journal=Proceedings of the National Academy of Sciences  |volume=104 |issue=31 |pages=12843–12848 |doi=10.1073/pnas.0701466104 |doi-access=free |pmid=17646651 |via=PNAS|pmc=1937554 }}</ref> This alteration of expression may be moderated by the host's immune responses, such as parasitic activity and inflammation resulting from elevated [[TNF-α|TNF-α levels]].<ref name=":0222" />

====Neurological/Neurocognitive Symptoms====

Neurological symptoms include: [[tremor]], general muscle weakness, [[hemiparesis]], [[paralysis]] of a limb,<ref name="Brun10" /> abnormal muscle tone, gait disturbance, ataxia, speech disturbances, paraesthesia, hyperaesthesia, anaesthesia, visual disturbance, abnormal reflexes, seizures, and coma.<ref name="www.cdc.gov_2020" /> [[Parkinsonism|Parkinson]]-like movements might arise due to non-specific movement disorders and speech disorders.<ref name="Brun10" />

====Psychiatric/Behavioural symptoms====

Individuals may exhibit psychiatric symptoms, which can sometimes dominate the clinical presentation. These symptoms include aggressiveness, [[apathy]],<ref name="www.cdc.gov_2020" /><ref name="Brun10" /> irritability, [[Psychosis|psychotic]] reactions<ref name="Brun10">{{cite journal | vauthors = Brun R, Blum J, Chappuis F, Burri C | title = Human African trypanosomiasis | journal = Lancet | volume = 375 | issue = 9709 | pages = 148–159 | date = January 2010 | pmid = 19833383 | doi = 10.1016/S0140-6736(09)60829-1 | hdl-access = free | s2cid = 39433996 | hdl = 10144/114145 }}</ref> and [[hallucination]]s, [[anxiety]], [[emotional lability]], [[confusion]], [[mania]], attention deficit, and [[delirium]].<ref name="www.cdc.gov_2020" />